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V-fos FBJ murine osteosarcoma viral oncogene homolog

PDB rendering based on 1a02.
Available structures
1a02, 1fos, 1s9k
Symbols FOS; c-fos
External IDs OMIM164810 MGI95574 HomoloGene3844 GeneCards: FOS Gene
RNA expression pattern
PBB GE FOS 209189 at tn.png
More reference expression data
Species Human Mouse
Entrez 2353 14281
Ensembl ENSG00000170345 ENSMUSG00000021250
UniProt P01100 Q3U463
RefSeq (mRNA) NM_005252 NM_010234
RefSeq (protein) NP_005243 NP_034364
Location (UCSC) Chr 14:
74.82 - 74.82 Mb
Chr 12:
86.36 - 86.37 Mb
PubMed search [1] [2]

In the field of molecular biology, c-Fos is a protein that in humans is encoded by the FOS gene.[1]


Structure and function

c-Fos is a cellular proto-oncogene belonging to the immediate early gene family of transcription factors. c-Fos has a leucine-zipper DNA binding domain, and a transactivation domain at the C-terminus. Transcription of c-Fos is upregulated in response to many extracellular signals, e.g. growth factors. Additionally, phosphorylation by MAPK, PKA, PKC or cdc2 alters the activity and stability of c-Fos. Members of the Fos family dimerise with C-Jun to form the AP-1 transcription factor, which upregulates transcription of a diverse range of genes involved in everything from proliferation and differentiation to defense against invasion and cell damage.

Clinical significance

The AP-1 complex has been implicated in transformation and progression of cancer, and both Fos and Jun were first discovered in rat fibroblasts. Fos was discovered as the transforming gene of the FBJ MSV and jun as the oncogene from avian sarcoma virus 17 (junana = 17).

The viral homologue of c-Fos, v-Fos, is found in the retrovirus Finkel–Biskis–Jinkins murine osteogenic sarcoma virus.

At least one study has shown that acute treatment with LSD is linked with a marked upregulation of c-fos expression in mammals.[2]


Neuroscientists measure expression of c-fos as an indirect marker of neuronal activity because c-fos is often expressed when neurons fire action potentials.[3] If c-fos mRNA is upregulated in a neuron this indicates recent activity.[4]


C-Fos has been shown to interact with CSNK2A2,[5] Casein kinase 2, alpha 1,[5] BCL3,[6] DNA damage-inducible transcript 3,[7] Cofactor of BRCA1,[8] TATA binding protein,[9] RELA,[10] Nuclear receptor coactivator 1,[11][12] Nuclear receptor co-repressor 2,[13] RUNX2,[14][15] RUNX1,[14][15] C-jun[10][16][17][18][19][20][21] and Mothers against decapentaplegic homolog 3.[22]

Overview of signal transduction pathways involved in apoptosis.

See also


  1. ^ van Straaten F, Müller R, Curran T, Van Beveren C, Verma IM (June 1983). "Complete nucleotide sequence of a human c-onc gene: deduced amino acid sequence of the human c-fos protein". Proc. Natl. Acad. Sci. U.S.A. 80 (11): 3183–7. PMID 6574479.  
  2. ^ Nichols CD, Sanders-Bush E (May 2002). "A single dose of lysergic acid diethylamide influences gene expression patterns within the mammalian brain". Neuropsychopharmacology 26 (5): 634–42. doi:10.1016/S0893-133X(01)00405-5. PMID 11927188.  
  3. ^ VanElzakker M, Fevurly RD, Breindel T, Spencer RL (2008). "Environmental novelty is associated with a selective increase in Fos expression in the output elements of the hippocampal formation and the perirhinal cortex". Learn. Mem. 15 (12): 899–908. doi:10.1101/lm.1196508. PMID 19050162.  
  4. ^ Day HE, Kryskow EM, Nyhuis TJ, Herlihy L, Campeau S (September 2008). "Conditioned fear inhibits c-fos mRNA expression in the central extended amygdala". Brain Res. 1229: 137–46. doi:10.1016/j.brainres.2008.06.085. PMID 18634767.  
  5. ^ a b Yamaguchi, Y; Wada T, Suzuki F, Takagi T, Hasegawa J, Handa H (Aug. 1998). "Casein kinase II interacts with the bZIP domains of several transcription factors". Nucleic Acids Res. (ENGLAND) 26 (16): 3854–61. doi:10.1093/nar/26.16.3854. PMID 9685505.  
  6. ^ Na, S Y; Choi J E, Kim H J, Jhun B H, Lee Y C, Lee J W (Oct. 1999). "Bcl3, an IkappaB protein, stimulates activating protein-1 transactivation and cellular proliferation". J. Biol. Chem. (UNITED STATES) 274 (40): 28491–6. doi:10.1074/jbc.274.40.28491. PMID 10497212.  
  7. ^ Ubeda, M; Vallejo M, Habener J F (Nov. 1999). "CHOP enhancement of gene transcription by interactions with Jun/Fos AP-1 complex proteins". Mol. Cell. Biol. (UNITED STATES) 19 (11): 7589–99. PMID 10523647.  
  8. ^ Zhong, Hongjun; Zhu Jianhua, Zhang Hao, Ding Lihua, Sun Yan, Huang Cuifen, Ye Qinong (Dec. 2004). "COBRA1 inhibits AP-1 transcriptional activity in transfected cells". Biochem. Biophys. Res. Commun. (United States) 325 (2): 568–73. doi:10.1016/j.bbrc.2004.10.079. PMID 15530430.  
  9. ^ Metz, R; Bannister A J, Sutherland J A, Hagemeier C, O'Rourke E C, Cook A, Bravo R, Kouzarides T (Sep. 1994). "c-Fos-induced activation of a TATA-box-containing promoter involves direct contact with TATA-box-binding protein". Mol. Cell. Biol. (UNITED STATES) 14 (9): 6021–9. PMID 8065335.  
  10. ^ a b Yang, X; Chen Y, Gabuzda D (Sep. 1999). "ERK MAP kinase links cytokine signals to activation of latent HIV-1 infection by stimulating a cooperative interaction of AP-1 and NF-kappaB". J. Biol. Chem. (UNITED STATES) 274 (39): 27981–8. doi:10.1074/jbc.274.39.27981. PMID 10488148.  
  11. ^ Lee, S K; Na S Y, Jung S Y, Choi J E, Jhun B H, Cheong J, Meltzer P S, Lee Y C, Lee J W (Jun. 2000). "Activating protein-1, nuclear factor-kappaB, and serum response factor as novel target molecules of the cancer-amplified transcription coactivator ASC-2". Mol. Endocrinol. (UNITED STATES) 14 (6): 915–25. doi:10.1210/me.14.6.915. PMID 10847592.  
  12. ^ Lee, S K; Kim H J, Na S Y, Kim T S, Choi H S, Im S Y, Lee J W (Jul. 1998). "Steroid receptor coactivator-1 coactivates activating protein-1-mediated transactivations through interaction with the c-Jun and c-Fos subunits". J. Biol. Chem. (UNITED STATES) 273 (27): 16651–4. doi:10.1074/jbc.273.27.16651. PMID 9642216.  
  13. ^ Lee, S K; Kim J H, Lee Y C, Cheong J, Lee J W (Apr. 2000). "Silencing mediator of retinoic acid and thyroid hormone receptors, as a novel transcriptional corepressor molecule of activating protein-1, nuclear factor-kappaB, and serum response factor". J. Biol. Chem. (UNITED STATES) 275 (17): 12470–4. doi:10.1074/jbc.275.17.12470. PMID 10777532.  
  14. ^ a b Hess, J; Porte D, Munz C, Angel P (Jun. 2001). "AP-1 and Cbfa/runt physically interact and regulate parathyroid hormone-dependent MMP13 expression in osteoblasts through a new osteoblast-specific element 2/AP-1 composite element". J. Biol. Chem. (United States) 276 (23): 20029–38. doi:10.1074/jbc.M010601200. PMID 11274169.  
  15. ^ a b D'Alonzo, Richard C; Selvamurugan Nagarajan, Karsenty Gerard, Partridge Nicola C (Jan. 2002). "Physical interaction of the activator protein-1 factors c-Fos and c-Jun with Cbfa1 for collagenase-3 promoter activation". J. Biol. Chem. (United States) 277 (1): 816–22. doi:10.1074/jbc.M107082200. PMID 11641401.  
  16. ^ Ito, T; Yamauchi M, Nishina M, Yamamichi N, Mizutani T, Ui M, Murakami M, Iba H (Jan. 2001). "Identification of SWI.SNF complex subunit BAF60a as a determinant of the transactivation potential of Fos/Jun dimers". J. Biol. Chem. (United States) 276 (4): 2852–7. doi:10.1074/jbc.M009633200. PMID 11053448.  
  17. ^ Pognonec, P; Boulukos K E, Aperlo C, Fujimoto M, Ariga H, Nomoto A, Kato H (May. 1997). "Cross-family interaction between the bHLHZip USF and bZip Fra1 proteins results in down-regulation of AP1 activity". Oncogene (ENGLAND) 14 (17): 2091–8. doi:10.1038/sj.onc.1201046. PMID 9160889.  
  18. ^ Glover, J N; Harrison S C (Jan. 1995). "Crystal structure of the heterodimeric bZIP transcription factor c-Fos-c-Jun bound to DNA". Nature (ENGLAND) 373 (6511): 257–61. doi:10.1038/373257a0. PMID 7816143.  
  19. ^ Nomura, N; Zu Y L, Maekawa T, Tabata S, Akiyama T, Ishii S (Feb. 1993). "Isolation and characterization of a novel member of the gene family encoding the cAMP response element-binding protein CRE-BP1". J. Biol. Chem. (UNITED STATES) 268 (6): 4259–66. PMID 8440710.  
  20. ^ Finkel, T; Duc J, Fearon E R, Dang C V, Tomaselli G F (Jan. 1993). "Detection and modulation in vivo of helix-loop-helix protein-protein interactions". J. Biol. Chem. (UNITED STATES) 268 (1): 5–8. PMID 8380166.  
  21. ^ Venugopal, R; Jaiswal A K (Dec. 1998). "Nrf2 and Nrf1 in association with Jun proteins regulate antioxidant response element-mediated expression and coordinated induction of genes encoding detoxifying enzymes". Oncogene (ENGLAND) 17 (24): 3145–56. doi:10.1038/sj.onc.1202237. PMID 9872330.  
  22. ^ Zhang, Y; Feng X H, Derynck R (Aug. 1998). "Smad3 and Smad4 cooperate with c-Jun/c-Fos to mediate TGF-beta-induced transcription". Nature (ENGLAND) 394 (6696): 909–13. doi:10.1038/29814. PMID 9732876.  

Further reading

  • Murphy LC, Alkhalaf M, Dotzlaw H, et al. (1994). "Regulation of gene expression in T-47D human breast cancer cells by progestins and antiprogestins.". Hum. Reprod. 9 Suppl 1: 174–80. PMID 7962462.  
  • Pompeiano M, Cirelli C, Arrighi P, Tononi G (1997). "c-Fos expression during wakefulness and sleep.". Neurophysiologie clinique (Clinical neurophysiology) 25 (6): 329–41. doi:10.1016/0987-7053(96)84906-9. PMID 8904195.  
  • Herrera DG, Robertson HA (1997). "Activation of c-fos in the brain.". Prog. Neurobiol. 50 (2-3): 83–107. doi:10.1016/S0301-0082(96)00021-4. PMID 8971979.  
  • Velazquez Torres A, Gariglio Vidal P (2002). "[Possible role of transcription factor AP1 in the tissue-specific regulation of human papillomavirus]". Rev. Invest. Clin. 54 (3): 231–42. PMID 12183893.  

External links

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