Gene Symbol: Sfn
Description: stratifin
Alias: Mme1, Ywhas, 14-3-3 protein sigma, 14-3-3 sigma protein, tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein, sigma polypeptide
Species: mouse
Products:     Sfn

Top Publications

  1. Tassin M, Salzgeber B, Guenet J. Studies on "repeated epilation" mouse mutant embryos: I. Development of facial malformations. J Craniofac Genet Dev Biol. 1983;3:289-307 pubmed
    ..The compression increases at 15 and 16 days. However, complete epithelial fusions do not occur. In 18-day-old embryos, cystic malformations appear in the glosso muscular system. ..
  2. Li Q, Lu Q, Estepa G, Verma I. Identification of 14-3-3sigma mutation causing cutaneous abnormality in repeated-epilation mutant mouse. Proc Natl Acad Sci U S A. 2005;102:15977-82 pubmed
    ..By analyzing the candidate genes generated from gene-expression profiling, we identified a Sfn mutation in Er mice...
  3. Su Y, Hao Z, Hirao A, Yamamoto K, Lin W, Young A, et al. 14-3-3sigma regulates B-cell homeostasis through stabilization of FOXO1. Proc Natl Acad Sci U S A. 2011;108:1555-60 pubmed publisher
    ..Our results suggest that 14-3-3? maintains FOXO1 at a consistent level critical for normal B-cell antigen receptor signaling and B-cell survival. ..
  4. Guenet J, Salzgeber B, Tassin M. Repeated epilation: a genetic epidermal syndrome in mice. J Hered. 1979;70:90-4 pubmed
    ..Homozygotes die immediately after birth from acute respiratory distress and exhibit an hypoplastic epidermal syndrome associated with morphological modifications of the oral cavity and of the limbs. ..
  5. Herron B, Liddell R, Parker A, Grant S, Kinne J, Fisher J, et al. A mutation in stratifin is responsible for the repeated epilation (Er) phenotype in mice. Nat Genet. 2005;37:1210-2 pubmed
    Stratifin (Sfn, also called 14-3-3sigma) is highly expressed in differentiating epidermis and mediates cell cycle arrest. Sfn is repressed in cancer, but its function during development is uncharacterized...
  6. Yang H, Wen Y, Chen C, Lozano G, Lee M. 14-3-3 sigma positively regulates p53 and suppresses tumor growth. Mol Cell Biol. 2003;23:7096-107 pubmed
    ..These results defined an important p53 regulatory loop and suggested that 14-3-3 sigma expression can be considered for therapeutic intervention in cancers. ..
  7. Xin Y, Lu Q, Li Q. 14-3-3sigma controls corneal epithelial cell proliferation and differentiation through the Notch signaling pathway. Biochem Biophys Res Commun. 2010;392:593-8 pubmed publisher
    ..We conclude that 14-3-3sigma is critical for regulating corneal epithelial proliferation and differentiation by regulating Notch signaling activity. ..
  8. Cousins S, Rodrigues M, Brown K, Dale B. Abnormal corneal and eyelid development in the repeated epilation mouse. Lab Anim Sci. 1984;34:156-63 pubmed
    ..The results suggest defective regulation of the synthesis of cellular proteins and altered cell surface properties in the Er/Er ocular epithelia. ..
  9. Hong H, Jeon W, Kim S, Kim B. 14-3-3 ? is a new target up-regulated by transforming growth factor-?1 through a Smad3-dependent mechanism. Biochem Biophys Res Commun. 2013;432:193-7 pubmed publisher
    ..Our data provides the first evidence that 14-3-3 ? is a Smad3-dependent target gene of TGF-?1. ..

More Information


  1. Ling C, Zuo D, Xue B, Muthuswamy S, Muller W. A novel role for 14-3-3sigma in regulating epithelial cell polarity. Genes Dev. 2010;24:947-56 pubmed publisher
    ..Taken together, these observations suggest that 14-3-3sigma plays a critical role in retaining epithelial polarity. ..
  2. Rountree R, Willis C, Dinh H, Blumberg H, Bailey K, Dean C, et al. RIP4 regulates epidermal differentiation and cutaneous inflammation. J Invest Dermatol. 2010;130:102-12 pubmed publisher
    ..many phenotypic similarities with inhibitor kappaB kinase (IKK)alpha(-/-) mice and stratifin repeated epilation (Sfn(Er/Er)) mice, the K14-RIP4 transgene failed to promote epidermal differentiation in these mutant backgrounds...
  3. Liang X, Peters K, Butterworth M, Frizzell R. 14-3-3 isoforms are induced by aldosterone and participate in its regulation of epithelial sodium channels. J Biol Chem. 2006;281:16323-32 pubmed
    ..Our studies show that aldosterone increases the expression of 14-3-3beta, which interacts with phospho-Nedd4-2 to block its interaction with ENaC, thus enhancing sodium absorption by increasing apical membrane ENaC density. ..
  4. Li Q, Sambandam S, Lu H, Thomson A, Kim S, Lu H, et al. 14-3-3? and p63 play opposing roles in epidermal tumorigenesis. Carcinogenesis. 2011;32:1782-8 pubmed publisher
    ..This study shows that p63 and 14-3-3? play opposing roles in the development of skin tumors and that the accumulation of p63 is essential for Ras/14-3-3? mutation-induced papilloma formation and squamous cell carcinoma carcinogenesis. ..
  5. LeBoeuf M, Terrell A, Trivedi S, Sinha S, Epstein J, Olson E, et al. Hdac1 and Hdac2 act redundantly to control p63 and p53 functions in epidermal progenitor cells. Dev Cell. 2010;19:807-18 pubmed publisher
    ..Our data identify critical requirements for HDAC1/2 in epidermal development and indicate that HDAC1/2 directly mediate repressive functions of p63 and suppress p53 activity. ..
  6. Richardson R, Dixon J, Malhotra S, Hardman M, Knowles L, Boot Handford R, et al. Irf6 is a key determinant of the keratinocyte proliferation-differentiation switch. Nat Genet. 2006;38:1329-34 pubmed
    ..are compound heterozygotes for mutations in Irf6 and the gene encoding the cell cycle regulator protein stratifin (Sfn; also known as 14-3-3sigma) show similar defects of keratinizing epithelia...
  7. Yang H, Zhang Y, Zhao R, Wen Y, Fournier K, Wu H, et al. Negative cell cycle regulator 14-3-3sigma stabilizes p27 Kip1 by inhibiting the activity of PKB/Akt. Oncogene. 2006;25:4585-94 pubmed
    ..These data provide an insight into 14-3-3sigma activity and rational cancer gene therapy by identifying 14-3-3sigma as a positive regulator of p27 and as a potential anticancer agent. ..
  8. Blackburn J, Ohazama A, Kawasaki K, Otsuka Tanaka Y, Liu B, Honda K, et al. The role of Irf6 in tooth epithelial invagination. Dev Biol. 2012;365:61-70 pubmed publisher
    ..Irf6 thus also plays a critical role in regulating epithelial invagination. In addition, we also found that canonical Wnt signaling is upregulated in evaginated incisor epithelium of both Ikk? and Irf6 mutant embryos. ..
  9. Xin Y, Lu Q, Li Q. 14-3-3sigma is required for club hair retention. J Invest Dermatol. 2010;130:1934-6 pubmed publisher
  10. Günschmann C, Stachelscheid H, Akyuz M, Schmitz A, Missero C, Bruning J, et al. Insulin/IGF-1 controls epidermal morphogenesis via regulation of FoxO-mediated p63 inhibition. Dev Cell. 2013;26:176-87 pubmed publisher
    ..Collectively, the present study reveals a critical role for IIS-dependent control of p63 activity in coordination of ACD and stratification during epithelial morphogenesis. ..
  11. Hong H, Jeon W, Bae E, Kim S, Lee H, Kim S, et al. 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;29:305-9 pubmed publisher
    ..Taken together, our findings indicate that dysregulation of 14-3-3 sigma or 14-3-3 zeta contributes to TGF-beta1 resistance in cancer cells. ..
  12. Sambandam S, Kasetti R, Xue L, Dean D, Lu Q, Li Q. 14-3-3σ regulates keratinocyte proliferation and differentiation by modulating Yap1 cellular localization. J Invest Dermatol. 2015;135:1621-1628 pubmed publisher
  13. Winter M, Lodygin D, Verdoodt B, Hermeking H. Deletion of 14-3-3? sensitizes mice to DMBA/TPA-induced papillomatosis. Oncotarget. 2016;7:46862-46870 pubmed publisher
    ..14-3-3?/SFN/stratifin is frequently silenced in human epithelial cancers, and experimental down-regulation of 14-3-3? ..
  14. Jones A, Lehman P, Dale B. Altered retinoid distribution in the repeated epilation (Er) mutant mouse. J Craniofac Genet Dev Biol. 1992;12:63-75 pubmed
    ..These results strongly suggest that altered retinoid distribution is associated with, and may be responsible for, the altered epithelial differentiation in the Er mutant. ..
  15. Fisher C. Abnormal development in the skin of the pupoid fetus (pf/pf) mutant mouse: abnormal keratinization, recovery of a normal phenotype, and relationship to the repeated epilation (Er/Er) mutant mouse. Curr Top Dev Biol. 1987;22:209-34 pubmed
  16. Tashakori M, Zhang Y, Xiong S, You M, Lozano G. p53 Activity Dominates That of p73 upon Mdm4 Loss in Development and Tumorigenesis. Mol Cancer Res. 2016;14:56-65 pubmed publisher
    ..Genetic characterization of the Mdm4 and p73 interaction during development and tumorigenesis suggests new insight into the role of p53 family members, which may influence treatment options for patients. ..
  17. Ingraham C, Kinoshita A, Kondo S, Yang B, Sajan S, Trout K, et al. Abnormal skin, limb and craniofacial morphogenesis in mice deficient for interferon regulatory factor 6 (Irf6). Nat Genet. 2006;38:1335-40 pubmed
    ..Histological and gene expression analyses indicate that the primary defect is in keratinocyte differentiation and proliferation. This study describes a new role for an IRF family member in epidermal development. ..
  18. Sundberg J, Sundberg B, Beamer W. Comparison of chemical carcinogen skin tumor induction efficacy in inbred, mutant, and hybrid strains of mice: morphologic variations of induced tumors and absence of a papillomavirus cocarcinogen. Mol Carcinog. 1997;20:19-32 pubmed
    ..These observations indicate that numerous modifier genes but not papillomaviruses are involved in cutaneous chemical carcinogenesis. ..
  19. Chai J, Locke D, Ohta T, Greally J, Nicholls R. Retrotransposed genes such as Frat3 in the mouse Chromosome 7C Prader-Willi syndrome region acquire the imprinted status of their insertion site. Mamm Genome. 2001;12:813-21 pubmed
    ..The recent evolutionary acquisition of genes that adopt the same imprint as older, flanking genes indicates that the newly acquired genes become 'innocent bystanders' of a primary epigenetic signal causing imprinting in the PWS domain. ..
  20. Sadik G, Tanaka T, Kato K, Yamamori H, Nessa B, Morihara T, et al. Phosphorylation of tau at Ser214 mediates its interaction with 14-3-3 protein: implications for the mechanism of tau aggregation. J Neurochem. 2009;108:33-43 pubmed publisher
    ..Also as the phosphorylation at Ser214 is up-regulated in Alzheimer's disease brain, tau's interaction with 14-3-3 might be involved in the pathology of this disease. ..
  21. Vosseller K, Hansen K, Chalkley R, Trinidad J, Wells L, Hart G, et al. Quantitative analysis of both protein expression and serine / threonine post-translational modifications through stable isotope labeling with dithiothreitol. Proteomics. 2005;5:388-98 pubmed
    ..These results demonstate BEMAD is suitable for large-scale quantitative analysis of both protein expression and serine / threonine post-translational modifications. ..
  22. Xu Z, Fulop Z, Wu G, Pone E, Zhang J, Mai T, et al. 14-3-3 adaptor proteins recruit AID to 5'-AGCT-3'-rich switch regions for class switch recombination. Nat Struct Mol Biol. 2010;17:1124-35 pubmed publisher
    ..Finally, 14-3-3 proteins interacted directly with AID and enhanced AID-mediated in vitro DNA deamination, further emphasizing the important role of these adaptors in CSR. ..
  23. Hammond N, Headon D, Dixon M. The cell cycle regulator protein 14-3-3σ is essential for hair follicle integrity and epidermal homeostasis. J Invest Dermatol. 2012;132:1543-53 pubmed publisher
    The 14-3-3σ (Stratifin; Sfn) is a cell cycle regulator intimately involved in the program of epithelial keratinization...
  24. Lutzner M, Guenet J, Breitburd F. Multiple cutaneous papillomas and carcinomas that develop spontaneously in a mouse mutant, the repeated epilation heterozygote Er/+. J Natl Cancer Inst. 1985;75:161-6 pubmed
    ..The Er/+ mouse should serve as a useful model for the exploration of genetic factors in cutaneous squamous cell carcinomas in humans. ..
  25. Urano T, Saito T, Tsukui T, Fujita M, Hosoi T, Muramatsu M, et al. Efp targets 14-3-3 sigma for proteolysis and promotes breast tumour growth. Nature. 2002;417:871-5 pubmed
    ..These data provide an insight into the cell-cycle machinery and tumorigenesis of breast cancer by identifying 14-3-3 sigma as a target for proteolysis by Efp, leading to cell proliferation. ..
  26. Lonic A, Barry E, Quach C, Kobe B, Saunders N, Guthridge M. Fibroblast growth factor receptor 2 phosphorylation on serine 779 couples to 14-3-3 and regulates cell survival and proliferation. Mol Cell Biol. 2008;28:3372-85 pubmed publisher
    ..In this regard, we have identified conserved putative phosphotyrosine/phosphoserine motifs in the cytoplasmic domains of diverse cell surface receptors, suggesting that they may perform important functional roles beyond the FGFRs. ..
  27. Reichelt J, Magin T. Hyperproliferation, induction of c-Myc and 14-3-3sigma, but no cell fragility in keratin-10-null mice. J Cell Sci. 2002;115:2639-50 pubmed
    ..While those experiments were performed in human cultured keratinocytes, our data establish, that in vivo, K10 acts by an indirect control mechanism in trans. ..
  28. Richardson R, Hammond N, Coulombe P, Saloranta C, Nousiainen H, Salonen R, et al. Periderm prevents pathological epithelial adhesions during embryogenesis. J Clin Invest. 2014;124:3891-900 pubmed publisher
    ..mutations in the genes encoding IFN regulatory factor 6 (IRF6), IκB kinase-α (IKKα), and stratifin (SFN) exhibit abnormal epidermal development, and we determined that mutant animals exhibit dysfunctional periderm ..
  29. Zhu F, Xia X, Liu B, Shen J, Hu Y, Person M, et al. IKKalpha shields 14-3-3sigma, a G(2)/M cell cycle checkpoint gene, from hypermethylation, preventing its silencing. Mol Cell. 2007;27:214-27 pubmed
    ..Thus, IKKalpha protects the 14-3-3sigma locus from hypermethylation, which serves as a mechanism of maintaining genomic stability in keratinocytes. ..
  30. Lu Q, Xin Y, Ye F, Foulks G, Li Q. 14-3-3? controls corneal epithelium homeostasis and wound healing. Invest Ophthalmol Vis Sci. 2011;52:2389-96 pubmed publisher
    ..Corneal phenotypes were investigated in heterozygous repeated epilation (Er) mice carrying mutations in the sfn (14-3-3?) gene...
  31. Dale B, Jones A, Presland R, Adler D, Disteche C. Chromosomal localization of the retinol binding protein gene and its elimination as a candidate gene for the repeated epilation (Er) mutation in mice. J Craniofac Genet Dev Biol. 1992;12:76-81 pubmed
    ..This physical mapping confirms the recent assignment of the gene to chromosome 19 by linkage analysis. These results eliminate the RBP gene as a candidate gene for the defect in the Er mutation that maps to chromosome 4. ..
  32. Kim S, Wong P, Coulombe P. A keratin cytoskeletal protein regulates protein synthesis and epithelial cell growth. Nature. 2006;441:362-5 pubmed
    ..These findings reveal a new and unexpected role for the intermediate filament cytoskeleton in influencing cell growth and size by regulating protein synthesis. ..
  33. Kawasaki M, Kawasaki K, Oommen S, Blackburn J, Watanabe M, Nagai T, et al. Regional regulation of Filiform tongue papillae development by Ikk?/Irf6. Dev Dyn. 2016;245:937-46 pubmed publisher
    ..Developmental Dynamics 245:937-946, 2016. © 2016 Wiley Periodicals, Inc. ..
  34. Rorick N, Kinoshita A, Weirather J, Peyrard Janvid M, de Lima R, Dunnwald M, et al. Genomic strategy identifies a missense mutation in WD-repeat domain 65 (WDR65) in an individual with Van der Woude syndrome. Am J Med Genet A. 2011;155A:1314-21 pubmed publisher
    ..The expression and mutation data were consistent with the hypothesis that WDR65 was a novel gene involved in oral clefting. ..
  35. Fisher C. IKKalpha-/- mice share phenotype with pupoid fetus (pf/pf) and repeated epilation (Er/Er) mutant mice. Trends Genet. 2000;16:482-4 pubmed
  36. Peluso J, Pappalardo A. Progesterone regulates granulosa cell viability through a protein kinase G-dependent mechanism that may involve 14-3-3sigma. Biol Reprod. 2004;71:1870-8 pubmed
    ..These data suggest that 1) P4 regulates the phosphorylation status of 14-3-3sigma through a PKG-dependent pathway and 2) 14-3-3sigma plays a central and essential role in maintaining the viability of SIGCs. ..
  37. Hong H, Kohli K, Trivedi A, Johnson D, Stallcup M. GRIP1, a novel mouse protein that serves as a transcriptional coactivator in yeast for the hormone binding domains of steroid receptors. Proc Natl Acad Sci U S A. 1996;93:4948-52 pubmed
    ..Thus, in yeast, GRIP1 can serve as a coactivator, potentiating the transactivation functions in steroid receptor HBDs, possibly by acting as a bridge between HBDs of the receptors and the basal transcription machinery. ..
  38. Tebbi A, Levillayer F, Jouvion G, Fiette L, Soubigou G, Varet H, et al. Deficiency of multidrug resistance 2 contributes to cell transformation through oxidative stress. Carcinogenesis. 2016;37:39-48 pubmed publisher
    ..Our findings imply a close link between Mdr2 (-/-) -associated tumorigenesis and perturbation of these biological processes and suggest potential extrahepatic functions of Mdr2/MDR3. ..
  39. Lee S, Kong Y, Weatherbee S. Forward genetics identifies Kdf1/1810019J16Rik as an essential regulator of the proliferation-differentiation decision in epidermal progenitor cells. Dev Biol. 2013;383:201-13 pubmed publisher
  40. Laronga C, Yang H, Neal C, Lee M. Association of the cyclin-dependent kinases and 14-3-3 sigma negatively regulates cell cycle progression. J Biol Chem. 2000;275:23106-12 pubmed
    ..These findings define 14-3-3 sigma as a negative regulator of the cell cycle progression and suggest that it has an important function in preventing breast tumor cell growth. ..
  41. Dillon R, Brown S, Ling C, Shioda T, Muller W. An EGR2/CITED1 transcription factor complex and the 14-3-3sigma tumor suppressor are involved in regulating ErbB2 expression in a transgenic-mouse model of human breast cancer. Mol Cell Biol. 2007;27:8648-57 pubmed
  42. Chang T, Liu C, Hsing E, Liang S, Chi Y, Sung L, et al. 14-3-3? regulates ?-catenin-mediated mouse embryonic stem cell proliferation by sequestering GSK-3?. PLoS ONE. 2012;7:e40193 pubmed publisher
    ..14-3-3? is a novel target for embryonic stem cell expansion. ..
  43. Ling C, Su V, Zuo D, Muller W. Loss of the 14-3-3? tumor suppressor is a critical event in ErbB2-mediated tumor progression. Cancer Discov. 2012;2:68-81 pubmed publisher
  44. Holbrook K, Dale B, Brown K. Abnormal epidermal keratinization in the repeated epilation mutant mouse. J Cell Biol. 1982;92:387-97 pubmed
  45. Boudreau A, Tanner K, Wang D, Geyer F, Reis Filho J, Bissell M. 14-3-3? stabilizes a complex of soluble actin and intermediate filament to enable breast tumor invasion. Proc Natl Acad Sci U S A. 2013;110:E3937-44 pubmed publisher
    ..Our data suggest that the biology of this protein is important in cellular movement and is contingent on breast cancer subtype. ..
  46. Brunet A, Kanai F, Stehn J, Xu J, Sarbassova D, Frangioni J, et al. 14-3-3 transits to the nucleus and participates in dynamic nucleocytoplasmic transport. J Cell Biol. 2002;156:817-28 pubmed
    ..These results indicate that 14-3-3 can mediate the relocalization of nuclear ligands by several mechanisms that ensure complete sequestration of the bound 14-3-3 complex in the cytoplasm. ..
  47. Fisher C, Byers M, Iadarola M, Powers E. Patterns of epithelial expression of Fos protein suggest important role in the transition from viable to cornified cell during keratinization. Development. 1991;111:253-8 pubmed
    ..Our data suggest that the expression of Fos is intricately related to epithelial cell differentiation, specifically in relation to the process of cornification and cell death. ..