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14-3-3 Proteins Are on the Crossroads of Cancer, Aging, and Age-Related Neurodegenerative Disease

Xiaolan Fan, Lang Cui, Yao Zeng and 3 more

International Journal of Molecular Sciences · 2019 · Review · CC BY

doi:10.3390/ijms20143518

Abstract

14-3-3 proteins are a family of conserved regulatory adaptor molecules which are expressed in all eukaryotic cells. These proteins participate in a variety of intracellular processes by recognizing specific phosphorylation motifs and interacting with hundreds of target proteins. Also, 14-3-3 proteins act as molecular chaperones, preventing the aggregation of unfolded proteins under conditions of cellular stress. Furthermore, 14-3-3 proteins have been shown to have similar expression patterns in tumors, aging, and neurodegenerative diseases. Therefore, we put forward the idea that the adaptor activity and chaperone-like activity of 14-3-3 proteins might play a substantial role in the above-mentioned conditions. Interestingly, 14-3-3 proteins are considered to be standing at the crossroads of cancer, aging, and age-related neurodegenerative diseases. There are great possibilities to improve the above-mentioned diseases and conditions through intervention in the activity of the 14-3-3 protein family.

Full text

From PubMed Central, U.S. National Library of Medicine, as current on Oct 26, 2026. Paragraph numbers are ours, so an answer can point at one.

1. Introduction

Aging is followed by a gradual decline in the functions of multiple organ systems and an increase in the incidence of chronic diseases such as cancer, Type 2 diabetes, and Alzheimer’s disease (AD). Aging is also associated with considerable alterations in internal homeostasis, especially in the immune and endocrine systems, which play a significant role in cancer control. Therefore, aging and carcinogenesis are coupled to each other at the molecular level. By analyzing the transcriptomic data set covering 531 samples at five different time points of aging, Peer et al. found that the aging-associated changes in transcriptomic expression and the transformation characteristics of chronic degenerative diseases (cardiovascular, metabolic, and neurodegenerative diseases) are related to each other and are different from the gene expression characteristics associated with cancer. It seems that aging, chronic degenerative diseases, and tumors affect the human body via different directions. Interestingly, aging and cancer also share similar expression characteristics, for example, the genomic stability during aging and cancer follows a similar pattern at the transcriptome level and therapeutic interventions for one of these might allow dual benefits of anti-aging as well as cancer prevention. These strategies include, but are not limited to, caloric restriction, drug senolytics, and so on. Long-term caloric restriction has been shown to delay the development of aging-related diseases in rodents and primates, including cancer.

The 14-3-3 protein family is constituted by 28–33 kDa acidic proteins found in all eukaryotes. The 14-3-3 proteins are phosphorylated serine/threonine binding proteins that bind to a variety of kinases, phosphatases, transmembrane receptors, and transcription factors. Hundreds of 14-3-3 ligands have been reported in the human proteome. The 14-3-3 proteins are widely expressed, especially in the central nervous system (CNS), and plays a key role in development and disease progression. Playing a similar role as other domains in signaling networks, 14-3-3 proteins generally interact with proteins that are involved in one of the three major functions, i.e., regulation, localization, or catalysis. It is widely accepted that 14-3-3 proteins act in two ways: By acting as adaptors and by displaying chaperone-like activity. By interaction with its partners, 14-3-3 proteins regulate critical biological processes, such as cell proliferation, growth, and apoptosis. In addition, 14-3-3 proteins are also involved in the regulation of various tumors, metabolic diseases, and neurodegenerative diseases. The gist of this review article is that 14-3-3 proteins are consistently up- and down-regulated in tumors, aging, and neurodegenerative disease. This suggests that targeting 14-3-3 proteins with specific drug compounds may facilitate a common therapeutic approach against aging, neurodegenerative disease, and cancer.

2. The Structure of 14-3-3 Proteins

14-3-3 proteins are present in almost all eukaryotic cells. There are seven human 14-3-3 members according to the amino acid sequences (Table 1), while two isoforms in yeast and up to 13 isoforms in plants have been observed.

It is well-accepted that most isoforms of the 14-3-3 proteins can form and function as both homodimers and heterodimers, with an exception of the 14-3-3σ isoform, which preferentially forms homodimers. The crystal structures of all seven mammalian 14-3-3 isoforms are available, showing that homodimers or heterodimers of 14-3-3 proteins generally consist of 9 α-helices. Each monomer consists of a bundle of nine antiparallel helices (H1-H9). The 14-3-3 dimers form cup-shaped structures, with a large, negatively charged, central passage with a diameter of about 35 Å, a width of 35 Å, and a depth of 20 Å, containing two ligand-binding grooves. These grooves include the side chains of Lys49, Arg56, Arg127, and Tyr128 (residue numbering corresponds to the isoform of 14-3-3). The monomeric subunits form a dimer through their N-terminal helices and the linkage of the salt bridge connects the dimer between the first two helices of one monomer and the fourth helix of the other monomer. The dimers bind the target proteins by three consensus phosphopeptide sequences: Motif I (RSXpSXP), motif II (RX(Y/F)XpSXP), and motif III (pSX1-2–COOH), wherein pS represents a phosphorylated serine/threonine and X is any residue. These phosphopeptide binding sites are present in both monomer units of 14-3-3, therefore this protein can bind to both phosphopeptides simultaneously; they can be from the same target protein, or two different target proteins. Furthermore, 14-3-3 proteins serve as adaptors or linkers. Depending upon the phosphorylation state of their specific recognition partners, 14-3-3 proteins bind their targets in order to stabilize the structure, phosphorylate and control their targets at the degradation level, localize and distribute between the different cellular compartments, and ultimately modulate their own interactions with other proteins.

However, 14-3-3 proteins also have the chaperone-like activity, i.e. 14-3-3ζ has been reported to dissolve heat-aggregated citrate synthase in vitro and has also been shown to interact with the heat shock proteins (HSP), HSP70/HSP40 chaperone to promote its reactivation. This chaperon-like activity of the 14-3-3 family proteins is very different from the well-characterized phosphorylation-dependent interaction of 14-3-3 with multiple target proteins. Neither the phospho-serine binding groove nor the flexible C-terminal extension have been proven to be necessary for 14-3-3 chaperone activity. Regardless of the use of any model substrate, 14-3-3 monomeric forms generally have higher activity than the dimeric form. Studies by Sluchanko et al. have shown that exposure of the dimer interface may play a role in 14-3-3 proteins’ molecular chaperone mechanism. Joanna et al. reported that the N-terminal helices of 14-3-3zeta may also play a role in chaperone action, whereby a D21N mutation may provide the key to the chaperone activity. To summarize, the mechanism of 14-3-3 anti-aggregation activity appears to be similar to the unrelated small heat shock proteins (sHsps) and is independent of ATP. The N-terminal portion of 14-3-3 contains a hydrophobic region and hides the intrinsic barrier that is critical for protein dimerization and appears to be important for the development of unfolded/misfolded proteins. Many different factors that promote dimerization enhance the chaperone-like activity of 14-3-3.

3.1. Cancer

Much work has been dedicated to understand the role of 14-3-3 proteins in cancer. Because of the lack of significant catalytic activity, the contribution of 14-3-3 proteins to cancer is primarily related to the regulation of oncoproteins and tumor suppressor proteins. The detailed information regarding the regulation of different types of cancers by 14-3-3 protein isoforms has been summarized in Table 1.

As shown in Table 1, the majority of 14-3-3 isoforms are elevated in almost all types of tumors, except the σ isoform, which is down-regulated in some cancer types. In breast, gastric, prostate, lung, and liver cancers, an association is seen with elevated levels of most 14-3-3 isoforms, whereas in leukemia, renal, and glioma cancers, only few specific isoforms have been reported to exhibit abnormal expression. There are a large number of reports on the regulatory mechanisms about the ζ and σ isoforms in tumors (see Table 1), therefore, in the following paragraphs, we will discuss their detailed regulatory mechanism in cancers.

The ζ isoform among the 14-3-3 protein family is the one with most abundant research reports in a multitude of cancers. The 14-3-3ζ isoform is highly expressed in a variety of cancers, including breast, ovarian, prostate, lung, and stomach cancers. This high expression of 14-3-3ζ has been associated with (but not limited to) poor prognosis and resistance to these cancers. 14-3-3 promotes survival of cancer cells through either binding to the p85 regulatory subunit of PI3K and activating Akt, or inactivating the tumor suppressor genes p53 and p21.

The 14-3-3ζ isoform plays an important role in another important cancer signaling pathway, which is the Wnt5a/ROR1 signal transduction pathway, and promotes the migration and proliferation of chronic lymphocytic leukemia. The 14-3-3ζ isoform likely functions via binding to the FOXO3a transcription factor and facilitating its transport to the cytoplasm, which in turn results in the enhanced proliferation of tongue cancer cells. In breast cancer cells, 14-3-3ζ brings forth contextual changes of Smad partners from p53 to Gli2 and therefore facilitates the switch from the tumor suppressive function of TGFβ to its metastasis-promoting activity.

The 14-3-3σ isoform attracts particular attention, which is considered to be a tumor suppressor protein whose down-regulation has been frequently detected in tumor specimens of many types of cancer. Also, 14-3-3σ was found to be a potent tumor suppressor involved in ErbB2-driven breast cancer initiation and metastasis. There is evidence that correlates the low expression of 14-3-3σ to hypermethylation of the 14-3-3σ promoter, leading to gene silencing. The promoter regions of 14-3-3σ gene displayed abnormal methylation in breast, lung, liver, ovarian, bladder, and prostate cancers. Therefore, 14-3-3σ methylation can be used as a diagnostic indicator for these tumors. 14-3-3σ has also been shown to be involved in the regulation of the energy metabolism of cancer cells. 14-3-3σ targets c-Myc for ubiquitination and proteasome-mediated degradation to suppress tumor metabolic reprogramming. Recently, it has been shown that the 14-3-3ζ and 14-3-3σ isoforms play an opposite role in the regulation of tumor suppressor or metastasis-promoting functions of transforming growth factor beta (TGFβ) signaling during cancer. In short, the 14-3-3 proteins in cancers mostly work as adaptors to bind their phosphorylated target proteins to regulate the occurrence, development, metastasis, and invasion of tumors.

3.2. Age-Related Neurodegenerative Disease

The 14-3-3 proteins exhibit chaperone-like activity, wherein they contain a nuclear localization sequence (NLS) through which they can transport target proteins to the nucleus. The pathogenesis of certain neurological diseases, such as Alzheimer’s disease (AD), Parkinson’s disease (PD), amyotrophic lateral sclerosis (ALS), schizophrenia, and bipolar disorder involve misfolding and excessive aggregation of proteins. Because of their chaperone-like activity, 14-3-3 proteins may play a role in these disease states. In fact, 14-3-3 proteins are highly expressed in the brain, accounting for about 1% of the total amount of soluble brain proteins. Also, the 14-3-3 isoform-specific functional knock-out mice have shown some syndrome phenotypes. Multiple studies in 14-3-3 isoform-specific K/O mouse models, as summarized in Table 2, have been very helpful in understanding 14-3-3 isoform-specific functions in the brain. Looking at the chaperone-like activity of 14-3-3 proteins, it comes as no surprise to see their involvement in a number of neurological disorders.

The association of 14-3-3 proteins with neurodegenerative diseases is further strengthened by their presence in Lewy bodies (LBs) and neurofibrillary tangles (NFTs) of AD brain sections. Several 14-3-3 isoforms are able to interact with specific proteins involved either in PD, ASL, or AD (Figure 1).

3.2.1. Parkinson’s Disease

Most of the 14-3-3 proteins are capable of interacting with α-synuclein, which is a regulator of the mitogen-activated protein kinase (MAPK) pathway, and therefore play an important role in the synthesis of dopamine. Connotations between 14-3-3 (β and ε isoforms) and α-synuclein occurs either in cytosolic or membrane fractions of rat brain homogenate. In fact, 14-3-3 and α-synuclein can be obtained by co-immunoprecipitation in the mammalian brain. The 14-3-3η isoform strongly affect the products and the kinetics of α-synuclein aggregation in vitro by binding to α-synuclein oligomers. Overexpression of the 14-3-3η isoform results in reduced α-synuclein toxicity in cellular models. One possible mechanism for this could be that the 14-3-3 protein is sequestered by the interaction with α-synuclein, resulting in a loss of 14-3-3 function, which is involved in the pathogenesis of PD.

Besides the α-synuclein, the 14-3-3ζ isoform also binds and stimulates the activation of tyrosine hydroxylase (TH), the rate-limiting enzyme in the biosynthesis of catecholamine. The 14-3-3η isoform interacts with parkin, which is an ubiquitin E3 ligase, leading to protein degradation. The 14-3-3η–parkin association leads to the suppression of ubiquitin-ligase activity of parkin, which is one of the causes of PD.

LRRK2 and phosphorylated FOXO3a are also the interacting partners of 14-3-3 proteins. FOXO3a localizes in LBs and recently a hypothesis was proposed suggesting the formation of a complex, including FOXO3a, α-synuclein, and 14-3-3 proteins, which promotes cell survival.

3.2.2. Alzheimer’s Disease

Tau is a major microtubule-associated protein in neurons, which can bind and stabilize microtubules. Tau phosphorylation reduces its affinity for microtubules and it is reported that tau is hyperphosphorylated in AD. 14-3-3 proteins have been detected in NFT of AD patients, with 14-3-3ζ being the most immuno-reactive. Further study has demonstrated that 14-3-3ζ facilitates GSK3β-dependent phosphorylation of tau by enhancing the affinity of GSK3β for tau. The 14-3-3ζ isoform also binds to δ-catenin, a brain protein first discovered in the interaction with presenilin 1.

In addition to the evidence of specific interactions with proteins associated to neurodegenerative diseases, 14-3-3 proteins also exhibit protective effects on dopaminergic neurons. Indeed, 14-3-3θ, γ, and ε isoforms reduce the cellular toxicity induced by neurotoxins, causing cell death in dopaminergic cells. It has also been suggested that 14-3-3 proteins may be involved in the chelation and degradation of toxic oligomers and aggregates by promoting the formation of aggresomes. Recently, 14-3-3 proteins recognized phosphorylated transcription factor EB (TFEB) and affected the autophagy, which is strongly correlated with neurodegenerative disease. Thus, looking at the functions of 14-3-3 proteins in age-related neurodegenerative disease, the potential development of drugs to therapeutically target 14-3-3 protein-protein interactions (PPIs) could be a good approach for the treatment of these kinds of diseases.

4. Aging Process

The 14-3-3 proteins are shown to be involved in many metabolic and autophagy regulatory pathways, such as Insulin/insulin-like growth factor signalling (IIS), AMP-activated protein kinase (AMPK), mechanistic target of rapamycin (mTOR) and MAPK, and these pathways play direct roles in the aging process. Thus, the 14-3-3 protein family may play a role in regulation of aging. The first study to explore the involvement of the 14-3-3 protein family on the lifespan regulation was carried out on C. elegans. Wang et al. found that in lifespan regulation, 14-3-3 proteins were co-expressed with DAF-16 and SIR-2.1 and DAF-16/ Forkhead box O (FOXO) interacted physically with 14-3-3 proteins, suggesting that in C. elegans, the 14-3-3 protein regulate the lifespan by synergy with SIR-2.1 and DAF-16/FOXO. In another report, Berdichevsky et al. demonstrated that SIR-2.1 and 14-3-3 activated DAF16 and extended the life span in a stress-dependent pathway in C. elegans. Also, 14-3-3 proteins promoted the life span by both FOXO/daf16-dependent and independent manners. To sum up, the role of 14-3-3 proteins in lifespan regulation in C. elegans is mostly by interacting with FOXO/DAF16.

In Drosophila, there are two isoforms of proteins, ε and ζ. Nielsen and colleagues found that the mutations in 14-3-3ε resulted in increased stress-induced apoptosis, growth inhibition, and prolonged lifespan, which were associated with increased FOXO activity. Both 14-3-3 protein isoforms regulated two interacting components of mTOR signaling in Drosophila and regulated the translation of tumor protein (Tctp) and Rheb GTPase during organ growth. It is already well-known that FOXO and TOR are two proteins that participate extensively in the aging process. Therefore, it can be stated that 14-3-3 proteins participate in the lifespan by regulating the activity of these longevity proteins in Drosophila.

The 14-3-3 proteins have also been reported to participate in the process of metabolic diseases, such as obesity and diabetes. The 14-3-3 protein interaction partner, heart-isomerized phospho-fructose-2-kinase/fructose-2,6-bisphosphatase (PFK-2), is involved in gluconeogenesis and glycolysis. 14-3-3β and 14-3-3γ have been reported to participate in human PPARγ2 transactivation and hepatic lipid metabolism. 14-3-3ζ and 14-3-3γ have been reported to be elevated in visceral and subcutaneous adipose tissue of obese individuals. 14-3-3ζ-overexpressing mice had significantly higher body weights and fat masses when fed a high fat diet. Significant changes in RNA and protein levels of 14-3-3ζ, ε, θ, and η in a murine model of Type 1 diabetes mellitus (T1DM) were detected. Thus, it can be put forth that 14-3-3 proteins contribute to the development of metabolic diseases.

In Saccharomyces cerevisiae, upon deleting the 14-3-3 protein, Bmh1 increased the stress response and prolonged the lifespan. The isoform β negatively regulated the glioblastoma cells senescence via the ERK-SKP2-p27 pathway. The 14-3-3η protein and the downstream MAPK were thought to be effective in age-related cardiac dysfunction. Network analyses have shown that skin aging triggered significant downregulation of 14-3-3 sigma. Therefore, it can be firmly stated that 14-3-3 proteins play a very important regulatory role during aging.

5. Conclusions and Challenges

The 14-3-3 protein family plays a major role in aging, cancer, and aging-related neurodegenerative disease. During these disease states, the majority of the 14-3-3 proteins are up-regulated. This means a careful reduction of 14-3-3 activity in these processes or diseases may be beneficial in alleviating the relevant phenotype. However, the activity of 14-3-3 in regulating tumors and neurological diseases is slightly different (Figure 2). In tumors, 14-3-3 proteins play the role of adaptors by regulating the phosphorylation of the target sites in order to regulate protein activity, proliferation, apoptosis, metastasis, and survival of tumor cells. All of this regulation is predominantly based on the presence of a special phosphopeptide-binding amphipathic groove and on the dimeric status of 14-3-3.

In neurological diseases, 14-3-3 proteins mostly exhibit chaperone-like activities to interact with the protein aggregates. This activity of 14-3-3 proteins prevent the aggregation of partially folded or misfolded proteins or pro-proteins, thereby protecting cells from the accumulation of potentially harmful oligomers of unfolded protein intermediates. Therefore, it represents an integral part of the overall cyto-protection system and this protection is mostly associated with the monomeric forms. Various factors (stress, drugs, aging, etc.; see Figure 2) can alter the balance between 14-3-3 protein dimers and their monomeric forms, thereby affecting their mode of action.

The members of the 14-3-3 protein family can bind hundreds of target proteins and perform essential roles in human development, health, and pathological processes. However, many challenges still exist around this protein family. As 14-3-3 proteins function as dimers and monomers, the 14-3-3 isoforms may have functional redundancy. Alterations in the specific isoform levels may thus have an indirect effect by changing the balance of the 14-3-3 proteins. Furthermore, due to the similarity of the 14-3-3 family protein structure, it is very challenging to specifically inhibit one isoform’s function. Strategies to effectively regulate 14-3-3 activity need to be developed in order to utilize them as therapeutic candidates.

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    Wang Z., Nesland J.M., Suo Z., Trope C.G., Holm R. The prognostic value of 14-3-3 isoforms in vulvar squamous cell carcinoma cases: 14-3-3beta and epsilon are independent prognostic factors for these tumors. PLoS ONE. 2011;6:e24843.

    Not in our library10.1371/journal.pone.0024843

  43. 43.

    Liang S., Xu Y., Shen G., Liu Q., Zhao X., Xu Z., Xie X., Gong F., Li R., Wei Y. Quantitative protein expression profiling of 14-3-3 isoforms in human renal carcinoma shows 14-3-3 epsilon is involved in limitedly increasing renal cell proliferation. Electrophoresis. 2009;30:4152-4162.

    Not in our library10.1002/elps.200900249

  44. 44.

    Ko B.S., Chang T.C., Hsu C., Chen Y.C., Shen T.L., Chen S.C., Wang J., Wu K.K., Jan Y.J., Liou J.Y. Overexpression of 14-3-3epsilon predicts tumour metastasis and poor survival in hepatocellular carcinoma. Histopathology. 2011;58:705-711.

    Not in our library10.1111/j.1365-2559.2011.03789.x

  45. 45.

    Qi W., Liu X., Qiao D., Martinez J.D. Isoform-specific expression of 14-3-3 proteins in human lung cancer tissues. Int. J. Cancer. 2005;113:359-363.

    Not in our library10.1002/ijc.20492

  46. 46.

    Gong X., Yan L., Gu H., Mu Y., Tong G., Zhang G. 14-3-3ε functions as an oncogene in SGC7901 gastric cancer cells through involvement of cyclin E and p27kip1. Mol. Med. Rep. 2014;10:3145-3150.

    Not in our library10.3892/mmr.2014.2605

  47. 47.

    Ko B.S., Lai I.R., Chang T.C., Liu T.A., Chen S.C., Wang J., Jan Y.J., Liou J.Y. Involvement of 14-3-3γ overexpression in extrahepatic metastasis of hepatocellular carcinoma. Hum. Pathol. 2011;42:129-135.

    Not in our library10.1016/j.humpath.2010.01.028

  48. 48.

    Hiraoka E., Mimae T., Ito M., Kadoya T., Miyata Y., Ito A., Okada M. Breast cancer cell motility is promoted by 14-3-3γ. Breast Cancer. 2019.

    Not in our library10.1007/s12282-019-00957-4

  49. 49.

    Qi W., Liu X., Chen W., Li Q., Martinez J.D. Overexpression of 14-3-3gamma causes polyploidization in H322 lung cancer cells. Mol. Carcinog. 2007;46:847-856.

    Not in our library10.1002/mc.20314

  50. 50.

    Titus M.A., Tan J.A., Gregory C.W., Ford O.H., Subramanian R.R., Fu H., Wilson E.M., Mohler J.L., French F.S. 14-3-3{eta} amplifies androgen receptor actions in prostate cancer. Clin. Cancer Res.: An Off. J. Am. Assoc. Cancer Res. 2009;15:7571-7581.

    Not in our library10.1158/1078-0432.ccr-08-1976

  51. 51.

    Li X.H., Noguchi A., Nishida T., Takahashi H., Zheng Y., Yang X.H., Masuda S., Kikuchi K., Takano Y. Cytoplasmic expression of p33ING1b is correlated with tumorigenesis and progression of head and neck squamous cell carcinoma. Histol. Histopathol. 2011;26:597-607.

    Not in our library10.14670/hh-26.597

  52. 52.

    Park G.Y., Han J.Y., Han Y.K., Kim S.D., Kim J.S., Jo W.S., Chun S.H., Jeong D.H., Lee C.W., Yang K., et al. 14-3-3 eta depletion sensitizes glioblastoma cells to irradiation due to enhanced mitotic cell death. Cancer Gene Ther. 2014;21:158-163.

    Not in our library10.1038/cgt.2014.11

  53. 53.

    Xiao Y., Lin V.Y., Ke S., Lin G.E., Lin F.T., Lin W.C. 14-3-3tau promotes breast cancer invasion and metastasis by inhibiting RhoGDI alpha. Mol. Cell Biol. 2014;34:2635-2649.

    Not in our library10.1128/mcb.00076-14

  54. 54.

    Lee T.G., Jeong E.H., Kim S.Y., Kim H.R., Kim H., Kim C.H. Fhit, a tumor suppressor protein, induces autophagy via 14-3-3tau in non-small cell lung cancer cells. Oncotarget. 2017;8:31923-31937.

    Not in our library10.18632/oncotarget.16652

  55. 55.

    Yan Y., Xu Y., Gao Y.Y., Zong Z.H., Zhang Q., Li C., Wang H.Q. Implication of 14-3-3epsilon and 14-3-3theta/tau in proteasome inhibition-induced apoptosis of glioma cells. Cancer Sci. 2013;104:55-61.

    Not in our library10.1111/cas.12033

  56. 56.

    Obsilova V., Silhan J., Boura E., Teisinger J., Obsil T. 14-3-3 proteins: A family of versatile molecular regulators. Physiol Res. 2008;57:S11-S21.

    Not in our library10.33549/physiolres.931598

  57. 57.

    Bridges D., Moorhead G.B. 14-3-3 proteins: A number of functions for a numbered protein. Sci. STKE. 2005;2005:re10.

    Not in our library10.1126/stke.2962005re10

  58. 58.

    Wilker E.W., Grant R.A., Artim S.C., Yaffe M.B. A structural basis for 14-3-3sigma functional specificity. J. Biol. Chem. 2005;280:18891-18898.

    Not in our library10.1074/jbc.m500982200

  59. 59.

    Stevers L.M., Lam C.V., Leysen S.F., Meijer F.A., Scheppingen D.S., Vries R.M., Carlile G.W., Milroy L.G., Thomas D.Y., Brunsveld L., et al. Characterization and small-molecule stabilization of the multisite tandem binding between 14-3-3 and the R domain of CFTR. Proc. Natl. Acad. Sci. USA. 2016;113:1152-1161.

    Not in our library10.1073/pnas.1516631113

  60. 60.

    Yang X., Lee W.H., Sobott F., Papagrigoriou E., Robinson C.V., Grossmann J.G., Sundstrom M., Doyle D.A., Elkins J.M. Structural basis for protein-protein interactions in the 14-3-3 protein family. Proc. Natl. Acad. Sci. USA. 2006;103:17237-17242.

    Not in our library10.1073/pnas.0605779103

  61. 61.

    Gardino A.K., Smerdon S.J., Yaffe M.B. Structural determinants of 14-3-3 binding specificities and regulation of subcellular localization of 14-3-3-ligand complexes: A comparison of the X-ray crystal structures of all human 14-3-3 isoforms. Semin. Cancer Biol. 2006;16:173-182.

    Not in our library10.1016/j.semcancer.2006.03.007

  62. 62.

    Coblitz B., Wu M., Shikano S., Li M. C-terminal binding: An expanded repertoire and function of 14-3-3 proteins. FEBS Lett. 2006;580:1531-1535.

    Not in our library10.1016/j.febslet.2006.02.014

  63. 63.

    Yaffe M.B., Rittinger K., Volinia S., Caron P.R., Aitken A., Leffers H., Gamblin S.J., Smerdon S.J., Cantley L.C. The structural basis for 14-3-3: phosphopeptide binding specificity. Cell. 1997;91:961-971.

    Not in our library10.1016/s0092-8674(00)80487-0

  64. 64.

    Alblova M., Smidova A., Docekal V., Vesely J., Herman P., Obsilova V., Obsil T. Molecular basis of the 14-3-3 protein-dependent activation of yeast neutral trehalase Nth1. Proc. Natl. Acad. Sci. USA. 2017;114:E9811-E9820.

    Not in our library10.1073/pnas.1714491114

  65. 65.

    Ganguly S., Weller J.L., Ho A., Chemineau P., Malpaux B., Klein D.C. Melatonin synthesis: 14-3-3-dependent activation and inhibition of arylalkylamine N-acetyltransferase mediated by phosphoserine-205. Proc. Natl. Acad. Sci. USA. 2005;102:1222-1227.

    Not in our library10.1073/pnas.0406871102

  66. 66.

    Demmel L., Beck M., Klose C., Schlaitz A.L., Gloor Y., Hsu P.P., Havlis J., Shevchenko A., Krause E., Kalaidzidis Y., et al. Nucleocytoplasmic shuttling of the Golgi phosphatidylinositol 4-kinase Pik1 is regulated by 14-3-3 proteins and coordinates Golgi function with cell growth. Mol. Biol. Cell. 2008;19:1046-1061.

    Not in our library10.1091/mbc.e07-02-0134

  67. 67.

    Yano M., Nakamuta S., Wu X., Okumura Y., Kido H. A novel function of 14-3-3 protein: 14-3-3zeta is a heat-shock-related molecular chaperone that dissolves thermal-aggregated proteins. Mol. Biol. Cell. 2006;17:4769-4779.

    Not in our library10.1091/mbc.e06-03-0229

  68. 68.

    Williams D.M., Ecroyd H., Goodwin K.L., Dai H., Fu H., Woodcock J.M., Zhang L., Carver J.A. NMR spectroscopy of 14-3-3zeta reveals a flexible C-terminal extension: Differentiation of the chaperone and phosphoserine-binding activities of 14-3-3zeta. Biochem. J. 2011;437:493-503.

    Not in our library10.1042/bj20102178

  69. 69.

    Sluchanko N.N., Roman S.G., Chebotareva N.A., Gusev N.B. Chaperone-like activity of monomeric human 14-3-3zeta on different protein substrates. Arch. Biochem. Biophys. 2014;549:32-39.

    Not in our library10.1016/j.abb.2014.03.008

  70. 70.

    Sluchanko N.N., Artemova N.V., Sudnitsyna M.V., Safenkova I.V., Antson A.A., Levitsky D.I., Gusev N.B. Monomeric 14-3-3zeta has a chaperone-like activity and is stabilized by phosphorylated HspB6. Biochemistry. 2012;51:6127-6138.

    Not in our library10.1021/bi300674e

  71. 71.
    The 14-3-3η chaperone protein promotes antiviral innate immunity via facilitating MDA5 oligomerization and intracellular redistribution. · 2019
    Not checked
  72. 72.

    Woodcock J.M., Goodwin K.L., Sandow J.J., Coolen C., Perugini M.A., Webb A.I., Pitson S.M., Lopez A.F., Carver J.A. Role of salt bridges in the dimer interface of 14-3-3zeta in dimer dynamics, N-terminal alpha-helical order, and molecular chaperone activity. J. Biol. Chem. 2018;293:89-99.

    Not in our library10.1074/jbc.m117.801019

  73. 73.

    Neal C.L., Yu D. 14-3-3zeta as a prognostic marker and therapeutic target for cancer. Expert Opin. Ther. Targets. 2010;14:1343-1354.

    Not in our library10.1517/14728222.2010.531011

  74. 74.

    Neal C.L., Yao J., Yang W., Zhou X., Nguyen N.T., Lu J., Danes C.G., Guo H., Lan K.H., Ensor J., et al. 14-3-3zeta overexpression defines high risk for breast cancer recurrence and promotes cancer cell survival. Cancer Res. 2009;69:3425-3432.

    Not in our library10.1158/0008-5472.can-08-2765

  75. 75.

    Neal C.L., Xu J., Li P., Mori S., Yang J., Neal N.N., Zhou X., Wyszomierski S.L., Yu D. Overexpression of 14-3-3ζ in cancer cells activates PI3K via binding the p85 regulatory subunit. Oncogene. 2012;31:897-906.

    Not in our library10.1038/onc.2011.284

  76. 76.

    Lee J.J., Lee J.S., Cui M.N., Yun H.H., Kim H.Y., Lee S.H., Lee J.H. BIS targeting induces cellular senescence through the regulation of 14-3-3 zeta/STAT3/SKP2/p27 in glioblastoma cells. Cell Death Dis. 2014;5:e1537.

    Not in our library10.1038/cddis.2014.501

  77. 77.

    Yu J., Chen L., Chen Y., Hasan M.K., Ghia E.M., Zhang L., Wu R., Rassenti L.Z., Widhopf G.F., Shen Z., et al. Wnt5a induces ROR1 to associate with 14-3-3ζ for enhanced chemotaxis and proliferation of chronic lymphocytic leukemia cells. Leukemia. 2017;31:2608-2614.

    Not in our library10.1038/leu.2017.132

  78. 78.

    Xu J., Acharya S., Sahin O., Zhang Q., Saito Y., Yao J., Wang H., Li P., Zhang L., Lowery F.J., et al. 14-3-3ζ turns TGF-β’s function from tumor suppressor to metastasis promoter in breast cancer by contextual changes of Smad partners from p53 to Gli2. Cancer Cell. 2015;27:177-192.

    Not in our library10.1016/j.ccell.2014.11.025

  79. 79.

    Ling C., Su V.M., Zuo D., Muller W.J. Loss of the 14-3-3σ tumor suppressor is a critical event in ErbB2-mediated tumor progression. Cancer Discov. 2012;2:68-81.

    Not in our library10.1158/2159-8290.cd-11-0189

  80. 80.

    Umbricht C.B., Evron E., Gabrielson E., Ferguson A., Marks J., Sukumar S. Hypermethylation of 14-3-3 sigma (stratifin) is an early event in breast cancer. Oncogene. 2001;20:3348-3353.

    Not in our library10.1038/sj.onc.1204438

  81. 81.

    Vercoutter-Edouart A.S., Lemoine J., Le X., Bourhis, Louis H., Boilly B., Nurcombe V., Révillion F., Peyrat J.P., Hondermarck H. Proteomic analysis reveals that 14-3-3sigma is down-regulated in human breast cancer cells. Cancer Res. 2001;61:76-80.

    Not in our library

  82. 82.

    Radhakrishnan V.M., Jensen T.J., Cui H., Futscher B.W., Martinez J.D. Hypomethylation of the 14-3-3σ promoter leads to increased expression in non-small cell lung cancer. Genes Chromosomes Cancer. 2011;50:830-836.

    Not in our library10.1002/gcc.20904

  83. 83.

    Luo J., Feng J., Lu J., Wang Y., Tang X., Xie F., Li W. Aberrant methylation profile of 14-3-3 sigma and its reduced transcription/expression levels in Chinese sporadic female breast carcinogenesis. Med. Oncol. 2010;27:791-797.

    Not in our library10.1007/s12032-009-9287-8

  84. 84.

    Yi B., Tan S.X., Tang C.E., Huang W.G., Cheng A., Li C., Zhang P.F., Li M.Y., Li J.L., Yi H., et al. Inactivation of 14-3-3 sigma by promoter methylation correlates with metastasis in nasopharyngeal carcinoma. J. Cell. Biochem. 2009;106:858-866.

    Not in our library10.1002/jcb.22051

  85. 85.

    Raungrut P., Petjaroen P., Geater S.L., Keeratichananont W., Phukaoloun M., Suwiwat S., Thongsuksai P. Methylation of 14-3-3σ gene and prognostic significance of 14-3-3σ expression in non-small cell lung cancer. Oncology Lett. 2017;14:5257-5264.

    Not in our library10.3892/ol.2017.6881

  86. 86.

    Lodygin D., Hermeking H. Epigenetic silencing of 14-3-3sigma in cancer. Semin. Cancer Biol. 2006;16:214-224.

    Not in our library10.1016/j.semcancer.2006.03.008

  87. 87.

    Phan L., Chou P.C., Velazquez-Torres G., Samudio I., Parreno K., Huang Y., Tseng C., Vu T., Gully C., Su C.H., et al. The cell cycle regulator 14-3-3sigma opposes and reverses cancer metabolic reprogramming. Nat. Commun. 2015;6:7530.

    Not in our library10.1038/ncomms8530

  88. 88.

    Hong H.Y., Jeon W.K., Bae E.J., Kim S.T., Lee H.J., Kim S.J., Kim B.C. 14-3-3 sigma and 14-3-3 zeta plays an opposite role in cell growth inhibition mediated by transforming growth factor-beta 1. Mol. Cells. 2010;29:305-309.

    Not in our library10.1007/s10059-010-0037-8

  89. 89.

    Berg D., Holzmann C., Riess O. 14-3-3 proteins in the nervous system. Nat. Rev. Neurosci. 2003;4:752-762.

    Not in our library10.1038/nrn1197

  90. 90.

    Steinacker P., Aitken A., Otto M. 14-3-3 proteins in neurodegeneration. Semin. Cell Dev. Biol. 2011;22:696-704.

    Not in our library10.1016/j.semcdb.2011.08.005

  91. 91.

    Ge W.W., Volkening K., Leystra-Lantz C., Jaffe H., Strong M.J. 14-3-3 protein binds to the low molecular weight neurofilament (NFL) mRNA 3’ UTR. Mol. Cell Neurosci. 2007;34:80-87.

    Not in our library10.1016/j.mcn.2006.10.001

  92. 92.

    Cheah P.S., Ramshaw H.S., Thomas P.Q., Toyo-Oka K., Xu X., Martin S., Coyle P., Guthridge M.A., Stomski F., van den Buuse M., et al. Neurodevelopmental and neuropsychiatric behaviour defects arise from 14-3-3zeta deficiency. Mol. Psychiatry. 2012;17:451-466.

    Not in our library10.1038/mp.2011.158

  93. 93.

    Xu X., Jaehne E.J., Greenberg Z., McCarthy P., Saleh E., Parish C.L., Camera D., Heng J., Haas M., Baune B.T., et al. 14-3-3zeta deficient mice in the BALB/c background display behavioural and anatomical defects associated with neurodevelopmental disorders. Sci. Rep. 2015;5:12434.

    Not in our library10.1038/srep12434

  94. 94.

    Ikeda M., Hikita T., Taya S., Uraguchi-Asaki J., Toyo-oka K., Wynshaw-Boris A., Ujike H., Inada T., Takao K., Miyakawa T., et al. Identification of YWHAE, a gene encoding 14-3-3epsilon, as a possible susceptibility gene for schizophrenia. Hum. Mol. Genet. 2008;17:3212-3222.

    Not in our library10.1093/hmg/ddn217

  95. 95.

    Wachi T., Cornell B., Toyo-Oka K. Complete ablation of the 14-3-3epsilon protein results in multiple defects in neuropsychiatric behaviors. Behav. Brain Res. 2017;319:31-36.

    Not in our library10.1016/j.bbr.2016.11.016

  96. 96.

    Kim D.E., Cho C.H., Sim K.M., Kwon O., Hwang E.M., Kim H.W., Park J.Y. 14-3-3gamma Haploinsufficient Mice Display Hyperactive and Stress-sensitive Behaviors. Exp. Neurobiol. 2019;28:43-53.

    Not in our library10.5607/en.2019.28.1.43

  97. 97.

    Toyo-oka K., Wachi T., Hunt R.F., Baraban S.C., Taya S., Ramshaw H., Kaibuchi K., Schwarz Q.P., Lopez A.F., Wynshaw-Boris A. 14-3-3epsilon and zeta regulate neurogenesis and differentiation of neuronal progenitor cells in the developing brain. J. Neurosci. 2014;34:12168-12181.

    Not in our library10.1523/jneurosci.2513-13.2014

  98. 98.

    Cornell B., Toyo-oka K. Deficiency of 14-3-3epsilon and 14-3-3zeta by the Wnt1 promoter-driven Cre recombinase results in pigmentation defects. BMC Res. Notes. 2016;9:180.

    Not in our library10.1186/s13104-016-1980-z

  99. 99.

    Foote M., Qiao H., Graham K., Wu Y., Zhou Y. Inhibition of 14-3-3 Proteins Leads to Schizophrenia-Related Behavioral Phenotypes and Synaptic Defects in Mice. Biol. Psychiatry. 2015;78:386-395.

    Not in our library10.1016/j.biopsych.2015.02.015

  100. 100.

    Graham K., Zhang J., Qiao H., Wu Y., Zhou Y. Region-specific inhibition of 14-3-3 proteins induces psychomotor behaviors in mice. NPJ Schizophr. 2019;5:1.

    Not in our library10.1038/s41537-018-0069-1

  101. 101.

    Perez R.G., Waymire J.C., Lin E., Liu J.J., Guo F., Zigmond M.J. A role for alpha-synuclein in the regulation of dopamine biosynthesis. J. Neurosci. 2002;22:3090-3099.

    Not in our library10.1523/jneurosci.22-08-03090.2002

  102. 102.

    Ostrerova N., Petrucelli L., Farrer M., Mehta N., Choi P., Hardy J., Wolozin B. alpha-Synuclein shares physical and functional homology with 14-3-3 proteins. J. Neurosci. 1999;19:5782-5791.

    Not in our library10.1523/jneurosci.19-14-05782.1999

  103. 103.

    Xu J., Kao S.Y., Lee F.J., Song W., Jin L.W., Yankner B.A. Dopamine-dependent neurotoxicity of alpha-synuclein: A mechanism for selective neurodegeneration in Parkinson disease. Nat. Med. 2002;8:600-606.

    Not in our library10.1038/nm0602-600

  104. 104.

    Plotegher N., Kumar D., Tessari I., Brucale M., Munari F., Tosatto L., Belluzzi E., Greggio E., Bisaglia M., Capaldi S., et al. The chaperone-like protein 14-3-3eta interacts with human alpha-synuclein aggregation intermediates rerouting the amyloidogenic pathway and reducing alpha-synuclein cellular toxicity. Hum. Mol. Genet. 2014;23:5615-5629.

    Not in our library10.1093/hmg/ddu275

  105. 105.

    Wang J., Lou H., Pedersen C.J., Smith A.D., Perez R.G. 14-3-3zeta contributes to tyrosine hydroxylase activity in MN9D cells: Localization of dopamine regulatory proteins to mitochondria. J. Biol. Chem. 2009;284:14011-14019.

    Not in our library10.1074/jbc.m901310200

  106. 106.

    Sato S., Chiba T., Sakata E., Kato K., Mizuno Y., Hattori N., Tanaka K. 14-3-3eta is a novel regulator of parkin ubiquitin ligase. EMBO J. 2006;25:211-221.

    Not in our library10.1038/sj.emboj.7600774

  107. 107.

    Paisan-Ruiz C., Jain S., Evans E.W., Gilks W.P., Simon J., van der Brug M., Lopez de Munain A., Aparicio S., Gil A.M., Khan N., et al. Cloning of the gene containing mutations that cause PARK8-linked Parkinson’s disease. Neuron. 2004;44:595-600.

    Not in our library10.1016/j.neuron.2004.10.023

  108. 108.
    Ectopic localization of FOXO3a protein in Lewy bodies in Lewy body dementia and Parkinson's disease · 2009
    Not checked
  109. 109.

    Ehrenberg A.J., Nguy A.K., Theofilas P., Dunlop S., Suemoto C.K., Di Lorenzo Alho A.T., Leite R.P., Diehl Rodriguez R., Mejia M.B., Rub U., et al. Quantifying the accretion of hyperphosphorylated tau in the locus coeruleus and dorsal raphe nucleus: The pathological building blocks of early Alzheimer’s disease. Neuropathol. Appl. Neurobiol. 2017;43:393-408.

    Not in our library10.1111/nan.12387

  110. 110.

    Umahara T., Uchihara T., Tsuchiya K., Nakamura A., Iwamoto T., Ikeda K., Takasaki M. 14-3-3 proteins and zeta isoform containing neurofibrillary tangles in patients with Alzheimer’s disease. Acta Neuropathol. 2004;108:279-286.

    Not in our library10.1007/s00401-004-0885-4

  111. 111.

    McFerrin M.B., Chi X., Cutter G., Yacoubian T.A. Dysregulation of 14-3-3 proteins in neurodegenerative diseases with Lewy body or Alzheimer pathology. Ann. Clin. Transl. Neurol. 2017;4:466-477.

    Not in our library10.1002/acn3.421

  112. 112.

    Yuan Z., Agarwal-Mawal A., Paudel H.K. 14-3-3 binds to and mediates phosphorylation of microtubule-associated tau protein by Ser9-phosphorylated glycogen synthase kinase 3beta in the brain. J. Biol. Chem. 2004;279:26105-26114.

    Not in our library10.1074/jbc.m308298200

  113. 113.

    He Y., Han J.R., Chang O., Oh M., James S.E., Lu Q., Seo Y.W., Kim H., Kim K. 14-3-3varepsilon/zeta Affects the stability of delta-catenin and regulates delta-catenin-induced dendrogenesis. FEBS Open Bio. 2013;3:16-21.

    Not in our library10.1016/j.fob.2012.11.006

  114. 114.

    Zhou J., Liyanage U., Medina M., Ho C., Simmons A.D., Lovett M., Kosik K.S. Presenilin 1 interaction in the brain with a novel member of the Armadillo family. Neuroreport. 1997;8:2085-2090.

    Not in our library10.1097/00001756-199705260-00054

  115. 115.

    Ding H., Underwood R., Lavalley N., Yacoubian T.A. 14-3-3 inhibition promotes dopaminergic neuron loss and 14-3-3θ overexpression promotes recovery in the MPTP mouse model of Parkinson’s disease. Neuroscience. 2015;307:73-82.

    Not in our library10.1016/j.neuroscience.2015.08.042

  116. 116.

    Betarbet R., Sherer T.B., MacKenzie G., Garcia-Osuna M., Panov A.V., Greenamyre J.T. Chronic systemic pesticide exposure reproduces features of Parkinson’s disease. Nat. Neurosci. 2000;3:1301-1306.

    Not in our library10.1038/81834

  117. 117.

    Jia B., Wu Y., Zhou Y. 14-3-3 and aggresome formation: Implications in neurodegenerative diseases. Prion. 2014;8:173-177.

    Not in our library10.4161/pri.28123

  118. 118.

    Xu Y., Ren J., He X., Chen H., Wei T., Feng W. YWHA/14-3-3 proteins recognize phosphorylated TFEB by a noncanonical mode for controlling TFEB cytoplasmic localization. Autophagy. 2019;15:1017-1030.

    Not in our library10.1080/15548627.2019.1569928

  119. 119.

    Wang Y., Oh S.W., Deplancke B., Luo J., Walhout A.J., Tissenbaum H.A. C. elegans 14-3-3 proteins regulate life span and interact with SIR-2.1 and DAF-16/FOXO. Mech. Ageing Dev. 2006;127:741-747.

    Not in our library10.1016/j.mad.2006.05.005

  120. 120.

    Berdichevsky A., Viswanathan M., Horvitz H.R., Guarente L.C. elegans SIR-2.1 interacts with 14-3-3 proteins to activate DAF-16 and extend life span. Cell. 2006;125:1165-1177.

    Not in our library10.1016/j.cell.2006.04.036

  121. 121.

    Araiz C., Chateau M.T., Galas S. 14-3-3 regulates life span by both DAF-16-dependent and -independent mechanisms in Caenorhabditis elegans. Exp. Gerontol. 2008;43:505-519.

    Not in our library10.1016/j.exger.2008.03.001

  122. 122.

    Nielsen M.D., Luo X., Biteau B., Syverson K., Jasper H. 14-3-3 Epsilon antagonizes FoxO to control growth, apoptosis and longevity in Drosophila. Aging Cell. 2008;7:688-699.

    Not in our library10.1111/j.1474-9726.2008.00420.x

  123. 123.

    Le T.P., Vuong L.T., Kim A.R., Hsu Y.C., Choi K.W. 14-3-3 proteins regulate Tctp-Rheb interaction for organ growth in Drosophila. Nat. Commun. 2016;7:11501.

    Not in our library10.1038/ncomms11501

  124. 124.
    Long live FOXO : unraveling the role of FOXO proteins in aging and longevity · 2015
    No notice
  125. 125.

    Evans D.S., Kapahi P., Hsueh W.C., Kockel L. TOR signaling never gets old: Aging, longevity and TORC1 activity. Ageing Res. Rev. 2011;10:225-237.

    Not in our library10.1016/j.arr.2010.04.001

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    Kleppe R., Martinez A., Doskeland S.O., Haavik J. The 14-3-3 proteins in regulation of cellular metabolism. Semin. Cell Dev. Biol. 2011;22:713-719.

    Not in our library10.1016/j.semcdb.2011.08.008

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    Pozuelo M., Peggie M., Wong B.H., Morrice N., MacKintosh C. 14-3-3s regulate fructose-2, 6-bisphosphate levels by binding to PKB-phosphorylated cardiac fructose-2,6-bisphosphate kinase/phosphatase. EMBO J. 2003;22:3514-3523.

    Not in our library10.1093/emboj/cdg363

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    Park S., Yoo S., Kim J., An H.T., Kang M., Ko J. 14-3-3beta and gamma differentially regulate peroxisome proliferator activated receptor gamma2 transactivation and hepatic lipid metabolism. Biochim. Biophys. Acta. 2015;1849:1237-1247.

    Not in our library10.1016/j.bbagrm.2015.08.002

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    Insenser M., Montes-Nieto R., Vilarrasa N., Lecube A., Simo R., Vendrell J., Escobar-Morreale H.F. A nontargeted proteomic approach to the study of visceral and subcutaneous adipose tissue in human obesity. Mol. Cell Endocrinol. 2012;363:10-19.

    Not in our library10.1016/j.mce.2012.07.001

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    Lim G.E., Albrecht T., Piske M., Sarai K., Lee T.C., Ramshaw H.S., Sinha S., Guthridge M.A., Acker-Palmer A., Lopez A.F., et al. 14-3-3zeta coordinates adipogenesis of visceral fat. Nat. Commun. 2015;6:7671.

    Not in our library10.1038/ncomms8671

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    Taurino F., Stanca E., Vonghia L., Siculella L., Sardanelli A.M., Papa S., Zanotti F., Gnoni A. Short-term type-1 diabetes differentially modulates 14-3-3 proteins in rat brain and liver. Eur. J. Clin. Invest. 2014;44:350-358.

    Not in our library10.1111/eci.12241

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    Wang C., Skinner C., Easlon E., Lin S.J. Deleting the 14-3-3 protein Bmh1 extends life span in Saccharomyces cerevisiae by increasing stress response. Genetics. 2009;183:1373-1384.

    Not in our library10.1534/genetics.109.107797

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    Seo S.B., Lee J.J., Yun H.H., Im C.N., Kim Y.S., Ko J.H., Lee J.H. 14-3-3beta Depletion Drives a Senescence Program in Glioblastoma Cells Through the ERK/SKP2/p27 Pathway. Mol. Neurobiol. 2018;55:1259-1270.

    Not in our library10.1007/s12035-017-0407-8

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    Sreedhar R., Giridharan V.V., Arumugam S., Karuppagounder V., Palaniyandi S.S., Krishnamurthy P., Quevedo J., Watanabe K., Konishi T., Thandavarayan R.A. Role of MAPK-mediated endoplasmic reticulum stress signaling in the heart during aging in senescence-accelerated prone mice. BioFactors. 2016;42:368-375.

    Not in our library10.1002/biof.1280

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    Fang J.Y., Wang P.W., Huang C.H., Chen M.H., Wu Y.R., Pan T.L. Skin aging caused by intrinsic or extrinsic processes characterized with functional proteomics. Proteomics. 2016;16:2718-2731.

    Not in our library10.1002/pmic.201600141

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