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Gene Review

Fosl1  -  fos-like antigen 1

Mus musculus

Synonyms: AW538199, FRA-1, Fos-related antigen 1, Fra1, fra-1
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Disease relevance of Fosl1


Psychiatry related information on Fosl1

  • Fra1 is not expressed at any stage at or around the critical period of sex determination when Sry transcripts are present, thus excluding a role for Fra1 in sex determination and differentiation [6].

High impact information on Fosl1


Biological context of Fosl1


Anatomical context of Fosl1

  • Despite alterations in bone matrix proteins, ovariectomy induces high turnover bone loss in Fra1 Tg mice as in wildtype mice [2].
  • The expression of several bone matrix proteins, including matrix gla protein, is dysregulated in Fra1 Tg osteoblasts [2].
  • Further, we have examined the possibility that SRY may activate Fra1 during testis determination by analysing the expression of Fra1 in mouse fetal gonads [6].
  • Moreover, Fra-1 fails to substitute for c-Fos in inducing expression of target genes in fibroblasts [8].
  • Analysis of the transcription of different AP-1 members in various cell lines derived from tumors of epithelial origin revealed a correlation of fra-1 expression with mesenchymal characteristics of carcinoma cells [3].

Associations of Fosl1 with chemical compounds


Physical interactions of Fosl1

  • They also displayed increased AP1 DNA binding activity which was predominantly composed of cJun and Fra1 containing dimers [17].

Regulatory relationships of Fosl1

  • Furthermore, Fra-1 repressed AP-1 activity induced by either TPA or expression of c-Jun and c-Fos [18].
  • Overexpression of Fra-1 downregulated c-Jun and Nrf2 enhanced AP-1- and ARE-mediated reporter gene expression, respectively [19].

Other interactions of Fosl1

  • We conclude that oncogenic ras mediates the activation of the fra-1 gene which results in elevated AP-1 activity throughout the cell cycle [11].
  • Consequently, our results demonstrate that the Erk cascade plays a dual role in the co-ordinated regulation of the transcription and the phosphorylation of Fra-1 by insulin [12].
  • Analysis of the role of Amh and Fra1 in the Sry regulatory pathway [6].
  • In contrast, expression of c-Jun, Fra-1, Fra-2, and CREB mRNA was not affected by T3 [20].
  • Reduced expression of thrombospondins and craniofacial dysmorphism in mice overexpressing fra1 [2].

Analytical, diagnostic and therapeutic context of Fosl1


  1. Fosl1 is a transcriptional target of c-Fos during osteoclast differentiation. Matsuo, K., Owens, J.M., Tonko, M., Elliott, C., Chambers, T.J., Wagner, E.F. Nat. Genet. (2000) [Pubmed]
  2. Reduced expression of thrombospondins and craniofacial dysmorphism in mice overexpressing fra1. Nishiwaki, T., Yamaguchi, T., Zhao, C., Amano, H., Kurt, D.H., Bornstein, P., Toyama, Y., Matsuo, K. J. Bone Miner. Res. (2006) [Pubmed]
  3. Fra-1 induces morphological transformation and increases in vitro invasiveness and motility of epithelioid adenocarcinoma cells. Kustikova, O., Kramerov, D., Grigorian, M., Berezin, V., Bock, E., Lukanidin, E., Tulchinsky, E. Mol. Cell. Biol. (1998) [Pubmed]
  4. Increased bone formation and osteosclerosis in mice overexpressing the transcription factor Fra-1. Jochum, W., David, J.P., Elliott, C., Wutz, A., Plenk, H., Matsuo, K., Wagner, E.F. Nat. Med. (2000) [Pubmed]
  5. The Fos-related antigen Fra-1 is an activator of bone matrix formation. Eferl, R., Hoebertz, A., Schilling, A.F., Rath, M., Karreth, F., Kenner, L., Amling, M., Wagner, E.F. EMBO J. (2004) [Pubmed]
  6. Analysis of the role of Amh and Fra1 in the Sry regulatory pathway. Jeske, Y.W., Mishina, Y., Cohen, D.R., Behringer, R.R., Koopman, P. Mol. Reprod. Dev. (1996) [Pubmed]
  7. Distinct functions of junD in cardiac hypertrophy and heart failure. Ricci, R., Eriksson, U., Oudit, G.Y., Eferl, R., Akhmedov, A., Sumara, I., Sumara, G., Kassiri, Z., David, J.P., Bakiri, L., Sasse, B., Idarraga, M.H., Rath, M., Kurz, D., Theussl, H.C., Perriard, J.C., Backx, P., Penninger, J.M., Wagner, E.F. Genes Dev. (2005) [Pubmed]
  8. Fra-1 replaces c-Fos-dependent functions in mice. Fleischmann, A., Hafezi, F., Elliott, C., Remé, C.E., Rüther, U., Wagner, E.F. Genes Dev. (2000) [Pubmed]
  9. Fra-1 substitutes for c-Fos in AP-1-mediated signal transduction in retinal apoptosis. Wenzel, A., Iseli, H.P., Fleischmann, A., Hafezi, F., Grimm, C., Wagner, E.F., Remé, C.E. J. Neurochem. (2002) [Pubmed]
  10. SRY protein enhances transcription of Fos-related antigen 1 promoter constructs. Cohen, D.R., Sinclair, A.H., McGovern, J.D. Proc. Natl. Acad. Sci. U.S.A. (1994) [Pubmed]
  11. Attenuated expression of the serum responsive T1 gene in ras transformed fibroblasts due to the inhibition of c-fos gene activity. Kessler, R., Zacharova-Albinger, A., Laursen, N.B., Kalousek, M., Klemenz, R. Oncogene (1999) [Pubmed]
  12. Dual role for mitogen-activated protein kinase (Erk) in insulin-dependent regulation of Fra-1 (fos-related antigen-1) transcription and phosphorylation. Hurd, T.W., Culbert, A.A., Webster, K.J., Tavaré, J.M. Biochem. J. (2002) [Pubmed]
  13. Inhibition of activator protein 1 activity and cell growth by purified green tea and black tea polyphenols in H-ras-transformed cells: structure-activity relationship and mechanisms involved. Chung, J.Y., Huang, C., Meng, X., Dong, Z., Yang, C.S. Cancer Res. (1999) [Pubmed]
  14. Nicotine withdrawal up-regulates c-Fos transcription in pheochromocytoma cells. Ichino, N., Ishiguro, H., Yamada, K., Nishii, K., Sawada, H., Nagatsu, T. Neurosci. Res. (1999) [Pubmed]
  15. The gamma-glutamylcysteine synthetase and glutathione regulate asbestos-induced expression of activator protein-1 family members and activity. Shukla, A., Flanders, T., Lounsbury, K.M., Mossman, B.T. Cancer Res. (2004) [Pubmed]
  16. Isolation and characterization of murine fra-1: induction mediated by CD40 and surface Ig is protein kinase C dependent. Huo, L., Rothstein, T.L. J. Immunol. (1996) [Pubmed]
  17. Transformation by ras modifies AP1 composition and activity. Mechta, F., Lallemand, D., Pfarr, C.M., Yaniv, M. Oncogene (1997) [Pubmed]
  18. Antitumor promotion by phenolic antioxidants: inhibition of AP-1 activity through induction of Fra expression. Yoshioka, K., Deng, T., Cavigelli, M., Karin, M. Proc. Natl. Acad. Sci. U.S.A. (1995) [Pubmed]
  19. DEP-induced fra-1 expression correlates with a distinct activation of AP-1-dependent gene transcription in the lung. Zhang, Q., Kleeberger, S.R., Reddy, S.P. Am. J. Physiol. Lung Cell Mol. Physiol. (2004) [Pubmed]
  20. Rapid effects of triiodothyronine on immediate-early gene expression in Schwann cells. Mercier, G., Turque, N., Schumacher, M. Glia (2001) [Pubmed]
  21. Transactivation of Fra-1 and consequent activation of AP-1 occur extracellular signal-regulated kinase dependently. Young, M.R., Nair, R., Bucheimer, N., Tulsian, P., Brown, N., Chapp, C., Hsu, T.C., Colburn, N.H. Mol. Cell. Biol. (2002) [Pubmed]
  22. Placental vascularisation requires the AP-1 component fra1. Schreiber, M., Wang, Z.Q., Jochum, W., Fetka, I., Elliott, C., Wagner, E.F. Development (2000) [Pubmed]
  23. The transcription factor Fos-related antigen 1 is induced by thiazolidinediones during differentiation of 3T3-L1 cells. Albrektsen, T., Fleckner, J. Mol. Pharmacol. (2001) [Pubmed]
  24. Distribution of Fos- and Jun-related proteins and activator protein-1 composite factors in mouse brain induced by neuroleptics. Ozaki, T., Katsumoto, E., Mui, K., Furutsuka, D., Yamagami, S. Neuroscience (1998) [Pubmed]
  25. A highly conserved enhancer in mammalian type X collagen genes drives high levels of tissue-specific expression in hypertrophic cartilage in vitro and in vivo. Gebhard, S., Pöschl, E., Riemer, S., Bauer, E., Hattori, T., Eberspaecher, H., Zhang, Z., Lefebvre, V., de Crombrugghe, B., von der Mark, K. Matrix Biol. (2004) [Pubmed]
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