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Gene Review

Fosl2  -  fos-like antigen 2

Mus musculus

Synonyms: FRA-2, Fos-related antigen 2, Fra-2, Fra2
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Disease relevance of Fosl2


High impact information on Fosl2

  • This proliferative defect is associated with the markedly reduced induction of c-jun, c-fos, Fra-2 and FosB following activation of the CREBA119 transgenic thymocytes [4].
  • We have investigated the ability of Fos/Jun (a transcriptional activator involved in the signal transduction pathway) to interact with its cognate binding site located in the promoter region of the mouse fos-related antigen-2 (fra-2) promoter, when this site was reconstituted into a nucleosome [5].
  • This was associated with marked suppression of the nocturnal increase in fra-2 mRNA and protein levels, indicating that DNF2 expression inhibits downstream effects of Fra-2, including the maintenance of high levels of fra-2 gene expression [6].
  • In contrast, expression of Fra-1, Fra-2, and JunB and optimal expression of c-Jun are observed only with doses of LPA which induce sustained MAPK activation and DNA synthesis [7].
  • The coll2a1-Cre, Fosl2f/f mice die between 10 and 25 days after birth, are growth retarded and display smaller growth plates similar to Fosl2-/- embryos [8].

Chemical compound and disease context of Fosl2


Biological context of Fosl2


Anatomical context of Fosl2

  • Hence, Fra2 is a novel transcription factor important for skeletogenesis by affecting chondrocyte differentiation [8].
  • In addition, hypertrophic differentiation and ossification of primordial arches of the developing vertebrae are delayed in Fra2-deficient embryos [8].
  • The mouse Fra-2 protein showed 94% and 87.5% conservation with human and chicken Fra-2, respectively, and mouse Fra-2, like the chicken homolog, induced transformation of chicken embryo fibroblasts [12].
  • Opposing activities of c-Fos and Fra-2 on AP-1 regulated transcriptional activity in mouse keratinocytes induced to differentiate by calcium and phorbol esters [13].
  • Cyclic AMP stimulates a JunD/Fra-2 AP-1 complex and inhibits the proliferation of interleukin-6-dependent cell lines [11].

Associations of Fosl2 with chemical compounds


Physical interactions of Fosl2

  • Supershift EMSA revealed that VT preferentially induced JunB, JunD, phosphorylated c-Jun, c-Fos, and Fra-2 binding activities of the AP-1 family [18].

Regulatory relationships of Fosl2

  • MEKK1 regulates the AP-1 dimer repertoire via control of JunB transcription and Fra-2 protein stability [19].
  • Our findings suggest that upon onset of follicular recruitment, CREB-1 mediates FSH/cAMP signaling, which switches to cAMP-independent expression of P450scc in luteinizing granulosa cells expressing Fra-2 [20].

Other interactions of Fosl2

  • Fra-1 showed essentially the same transcriptional regulatory properties as Fra-2 [21].
  • Interestingly, this suppressive effect of Fra-2 was not observed in the combination with JunD: fra-2 plus junD, like c-fos plus junD, had higher transcriptional activity than junD alone [21].
  • AP-1 protein in nuclear extracts of MC3T3-E1 cells was increased with PTH treatment at 3 h and consisted of high levels of Fra-2 protein, as evidenced by a supershift in an electrophoretic mobility shift assay and Western blot analysis [22].
  • In contrast, expression of c-Jun, Fra-1, Fra-2, and CREB mRNA was not affected by T3 [23].
  • However, protein complexes from AtT-20 nuclear extracts that bound the GR AP-1 site were supershifted by JunD, JunB, cJun, and Fra-2 specific antibodies [24].

Analytical, diagnostic and therapeutic context of Fosl2


  1. Role of the Fos family members, c-Fos, Fra-1 and Fra-2, in the regulation of cell motility. Tkach, V., Tulchinsky, E., Lukanidin, E., Vinson, C., Bock, E., Berezin, V. Oncogene (2003) [Pubmed]
  2. Long-term induction of Fos-related antigen-2 after methamphetamine-, methylenedioxymethamphetamine-, 1-methyl-4-phenyl-1,2,3, 6-tetrahydropyridine- and trimethyltin-induced brain injury. Pennypacker, K.R., Yang, X., Gordon, M.N., Benkovic, S., Miller, D., O'Callaghan, J.P. Neuroscience (2000) [Pubmed]
  3. The transcription factor Fra-2 regulates the production of extracellular matrix in systemic sclerosis. Reich, N., Maurer, B., Akhmetshina, A., Venalis, P., Dees, C., Zerr, P., Palumbo, K., Zwerina, J., Nevskaya, T., Gay, S., Distler, O., Schett, G., Distler, J.H. Arthritis Rheum. (2010) [Pubmed]
  4. Defective thymocyte proliferation and IL-2 production in transgenic mice expressing a dominant-negative form of CREB. Barton, K., Muthusamy, N., Chanyangam, M., Fischer, C., Clendenin, C., Leiden, J.M. Nature (1996) [Pubmed]
  5. The binding of a Fos/Jun heterodimer can completely disrupt the structure of a nucleosome. Ng, K.W., Ridgway, P., Cohen, D.R., Tremethick, D.J. EMBO J. (1997) [Pubmed]
  6. Tissue-specific transgenic knockdown of Fos-related antigen 2 (Fra-2) expression mediated by dominant negative Fra-2. Smith, M., Burke, Z., Humphries, A., Wells, T., Klein, D., Carter, D., Baler, R. Mol. Cell. Biol. (2001) [Pubmed]
  7. The repertoire of fos and jun proteins expressed during the G1 phase of the cell cycle is determined by the duration of mitogen-activated protein kinase activation. Cook, S.J., Aziz, N., McMahon, M. Mol. Cell. Biol. (1999) [Pubmed]
  8. The AP1 transcription factor Fra2 is required for efficient cartilage development. Karreth, F., Hoebertz, A., Scheuch, H., Eferl, R., Wagner, E.F. Development (2004) [Pubmed]
  9. The gene encoding the Fos-related antigen 2 (Fosl2) maps to mouse chromosome 5. Poirier, C., Lalouette, A., Foletta, V.C., Cohen, D.R., Guénet, J.L. Mamm. Genome (1997) [Pubmed]
  10. 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]
  11. Cyclic AMP stimulates a JunD/Fra-2 AP-1 complex and inhibits the proliferation of interleukin-6-dependent cell lines. Rezzonico, R., Loubat, A., Lallemand, D., Pfarr, C.M., Far, D.F., Proudfoot, A., Rossi, B., Ponzio, G. Oncogene (1995) [Pubmed]
  12. Cloning and characterisation of the mouse fra-2 gene. Foletta, V.C., Sonobe, M.H., Suzuki, T., Endo, T., Iba, H., Cohen, D.R. Oncogene (1994) [Pubmed]
  13. Opposing activities of c-Fos and Fra-2 on AP-1 regulated transcriptional activity in mouse keratinocytes induced to differentiate by calcium and phorbol esters. Rutberg, S.E., Saez, E., Lo, S., Jang, S.I., Markova, N., Spiegelman, B.M., Yuspa, S.H. Oncogene (1997) [Pubmed]
  14. Possible role for the FosB/JunD AP-1 transcription factor complex in glutamate-mediated excitotoxicity in cultured cerebellar granule cells. Lidwell, K., Griffiths, R. J. Neurosci. Res. (2000) [Pubmed]
  15. Fra-2-positive autoregulatory loop triggered by mitogen-activated protein kinase (MAPK) and Fra-2 phosphorylation sites by MAPK. Murakami, M., Ui, M., Iba, H. Cell Growth Differ. (1999) [Pubmed]
  16. Roles of adenosine receptors in the regulation of kainic acid-induced neurotoxic responses in mice. Lee, H.K., Choi, S.S., Han, K.J., Han, E.J., Suh, H.W. Brain Res. Mol. Brain Res. (2004) [Pubmed]
  17. The antioxidant, rather than prooxidant, activities of quercetin on normal cells: quercetin protects mouse thymocytes from glucose oxidase-mediated apoptosis. Lee, J.C., Kim, J., Park, J.K., Chung, G.H., Jang, Y.S. Exp. Cell Res. (2003) [Pubmed]
  18. Effects of vomitoxin (deoxynivalenol) on the binding of transcription factors AP-1, NF-kappaB, and NF-IL6 in raw 264.7 macrophage cells. Wong, S.S., Zhou, H.R., Pestka, J.J. J. Toxicol. Environ. Health Part A (2002) [Pubmed]
  19. MEKK1 regulates the AP-1 dimer repertoire via control of JunB transcription and Fra-2 protein stability. Cuevas, B.D., Uhlik, M.T., Garrington, T.P., Johnson, G.L. Oncogene (2005) [Pubmed]
  20. Transcriptional Regulation of the Cholesterol Side Chain Cleavage Cytochrome P450 Gene (CYP11A1) Revisited: Binding of GATA, Cyclic Adenosine 3',5'-Monophosphate Response Element-Binding Protein and Activating Protein (AP)-1 Proteins to a Distal Novel Cluster of cis-Regulatory Elements Potentiates AP-2 and Steroidogenic Factor-1-Dependent Gene Expression in the Rodent Placenta and Ovary. Sher, N., Yivgi-Ohana, N., Orly, J. Mol. Endocrinol. (2007) [Pubmed]
  21. Difference in transcriptional regulatory function between c-Fos and Fra-2. Suzuki, T., Okuno, H., Yoshida, T., Endo, T., Nishina, H., Iba, H. Nucleic Acids Res. (1991) [Pubmed]
  22. Parathyroid hormone stimulates fra-2 expression in osteoblastic cells in vitro and in vivo. McCauley, L.K., Koh-Paige, A.J., Chen, H., Chen, C., Ontiveros, C., Irwin, R., McCabe, L.R. Endocrinology (2001) [Pubmed]
  23. Rapid effects of triiodothyronine on immediate-early gene expression in Schwann cells. Mercier, G., Turque, N., Schumacher, M. Glia (2001) [Pubmed]
  24. Occupancy and composition of proteins bound to the AP-1 sites in the glucocorticoid receptor and c-jun promoters after glucocorticoid treatment and in different cell types. Barrett, T.J., Vedeckis, W.V. Receptors & signal transduction. (1996) [Pubmed]
  25. Differential expression and phosphorylation of particular fos family members by kainate in nuclear and cytosolic fractions of murine hippocampus. Manabe, T., Kitayama, T., Ogita, K., Yoneda, Y. Neuroscience (2000) [Pubmed]
  26. Differential in vitro degradation of particular Fos family members expressed by kainic acid in nuclear and cytosolic fractions of murine hippocampus. Yoneda, Y., Nakamichi, N., Manabe, T., Ogita, K. J. Neurosci. Res. (2001) [Pubmed]
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