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Gene Review

Maf  -  avian musculoaponeurotic fibrosarcoma (v...

Mus musculus

Synonyms: 2810401A20Rik, A230108G15Rik, AW047063, Maf2, Proto-oncogene c-Maf, ...
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Disease relevance of Maf


High impact information on Maf


Biological context of Maf

  • We have used gene targeting to replace Maf coding sequences with those of lacZ, and have carried out a comprehensive analysis of embryonic expression and the homozygous mutant phenotype in the eye [10].
  • Our results indicate that Maf directly activates many if not all of the (beta)-crystallin genes, and suggest a model for coordinating cell cycle withdrawal with terminal differentiation [10].
  • Recombinant Maf protein binds to T-MARE sites in the (alpha)A-, (beta)B2-, and (beta)A4-crystallin promoters but fails to bind to a point mutation in the (alpha)A-crystallin promoter that has been shown previously to be required for promoter function [10].
  • Cyclosporin A and FK506, which target calcineurin and thereby inhibit TCR-mediated Ca(2+) signal pathways, block IL-6-mediated c-Maf expression [11].
  • Reporter transfection analysis using C3H10T1/2 cells shows that c-Maf stimulates a CTGF reporter gene [1].

Anatomical context of Maf

  • Maf is expressed in the lens vesicle after invagination, and becomes highly upregulated in the equatorial zone, the site at which self-renewing anterior epithelial cells withdraw from the cell cycle and terminally differentiate into posterior fiber cells [10].
  • Little is known about the mechanism that guides c-Maf regulation during early T cell activation [11].
  • As is the case for the c-maf gene, overexpression of the mafB gene induces transformation of chicken embryo fibroblasts in vitro [12].
  • We previously found that c-maf and mafB are strongly expressed in hypertrophic chondrocytes during cartilage development [1].
  • Our data indicate that c-maf is a common insertion site of MelARV in BL6, Meli-A1 and Meli-BL melanomas, whereas no such insertion site was found in the melanocytes infected with MelARV but not malignantly transformed [13].

Associations of Maf with chemical compounds

  • Gel shift assays using lens nuclear extracts demonstrated interactions of Pax6, Maf, and retinoic acid nuclear receptor proteins with two lens-specific regions, the distal LSR1 (-147/-118) and proximal LSR2 (-78/-40), of the alphaB-crystallin promoter [14].
  • Bach2 is a member of the BTB-basic region leucine zipper factor family and represses transcription activity directed by the 12-O-tetradecanoylphorbol-13-acetate response element, the Maf recognition element, and the antioxidant-responsive element [15].
  • Because MafA, MafB, and c-Maf were each capable of specifically binding to and activating insulin C1 element-mediated expression, our results suggest that all of these factors play a role in islet beta-cell function [16].
  • Oxidative stress abolishes leptomycin B-sensitive nuclear export of transcription repressor Bach2 that counteracts activation of Maf recognition element [17].
  • This protein controls the glucose-regulated and pancreatic beta-cell-specific expression of the insulin gene through a cis-regulatory element called RIPE3b/MARE (Maf-recognition element) [18].

Physical interactions of Maf

  • Heme mediates derepression of Maf recognition element through direct binding to transcription repressor Bach1 [19].
  • Electrophoresis mobility shift assay and DNase I footprinting analysis show that at least three Pax6-binding sites are located in the 5'-flanking and 5'-non-coding regions of the rat c-maf gene [20].
  • Bach2 is a B-cell-specific transcription repressor interacting with the small Maf proteins whose expression is high only before the plasma cell stage [21].
  • Impaired IL-4 production by CD8+ T cells in NOD mice is related to a defect of c-Maf binding to the IL-4 promoter [22].
  • In this study we sought to determine the identity of the specific constituent that collaboratively interacts with Nrf2 to bind to the Maf recognition element in vivo [23].

Regulatory relationships of Maf

  • IL-6 induces similar c-Maf expression in protein kinase Ctheta-deficient CD4(+) T cells [11].
  • We previously found that c-Maf, c-Jun, and Pax6 bind to and stimulate the c-maf gene [24].
  • Up-regulation of c-Maf was dependent on Ca2+/nuclear factor of activated T cell (NFAT) and, together with IL-4 production, could be rescued in Vav1-/- T cells by Ca2+ ionophore [25].
  • These results suggest that Bach2 regulates AP-1- and Maf-dependent gene expression during development of neuronal and lens cells and that its activity may be regulated by nuclear export in these cells [26].
  • MMP-13 is known to be regulated by AP-1 and may also be a target of c-Maf [27].

Other interactions of Maf

  • Through formation of numerous bZip dimers, the Maf family proteins along with the AP-1 components should provide great diversity in transcriptional regulation for a wide variety of genes [12].
  • Taken together, these data indicate that the CTGF gene is a target of c-Maf and Lc-Maf in cartilage development [1].
  • The transcription factor c-Maf plays a critical and selective role in IL-4 gene transcription [11].
  • Several transcription factors such as Pax6, Sox1, and L-Maf have been shown to regulate lens development [28].
  • Deficient IL-4 production was restored by retrovirus-mediated Vav1 expression, but only partially by retroviral c-Maf expression [25].

Analytical, diagnostic and therapeutic context of Maf


  1. Activation of connective tissue growth factor gene by the c-Maf and Lc-Maf transcription factors. Omoteyama, K., Ikeda, H., Imaki, J., Sakai, M. Biochem. Biophys. Res. Commun. (2006) [Pubmed]
  2. Sequence and insertion sites of murine melanoma-associated retrovirus. Li, M., Huang, X., Zhu, Z., Gorelik, E. J. Virol. (1999) [Pubmed]
  3. A dominant mutation within the DNA-binding domain of the bZIP transcription factor Maf causes murine cataract and results in selective alteration in DNA binding. Lyon, M.F., Jamieson, R.V., Perveen, R., Glenister, P.H., Griffiths, R., Boyd, Y., Glimcher, L.H., Favor, J., Munier, F.L., Black, G.C. Hum. Mol. Genet. (2003) [Pubmed]
  4. Small Maf compound mutants display central nervous system neuronal degeneration, aberrant transcription, and Bach protein mislocalization coincident with myoclonus and abnormal startle response. Katsuoka, F., Motohashi, H., Tamagawa, Y., Kure, S., Igarashi, K., Engel, J.D., Yamamoto, M. Mol. Cell. Biol. (2003) [Pubmed]
  5. Positive or negative MARE-dependent transcriptional regulation is determined by the abundance of small Maf proteins. Motohashi, H., Katsuoka, F., Shavit, J.A., Engel, J.D., Yamamoto, M. Cell (2000) [Pubmed]
  6. The proto-oncogene c-maf is responsible for tissue-specific expression of interleukin-4. Ho, I.C., Hodge, M.R., Rooney, J.W., Glimcher, L.H. Cell (1996) [Pubmed]
  7. Regulation of transcription by dimerization of erythroid factor NF-E2 p45 with small Maf proteins. Igarashi, K., Kataoka, K., Itoh, K., Hayashi, N., Nishizawa, M., Yamamoto, M. Nature (1994) [Pubmed]
  8. Impaired megakaryopoiesis and behavioral defects in mafG-null mutant mice. Shavit, J.A., Motohashi, H., Onodera, K., Akasaka, J., Yamamoto, M., Engel, J.D. Genes Dev. (1998) [Pubmed]
  9. The transcription factor c-Maf controls the production of interleukin-4 but not other Th2 cytokines. Kim, J.I., Ho, I.C., Grusby, M.J., Glimcher, L.H. Immunity (1999) [Pubmed]
  10. Regulation of mouse lens fiber cell development and differentiation by the Maf gene. Ring, B.Z., Cordes, S.P., Overbeek, P.A., Barsh, G.S. Development (2000) [Pubmed]
  11. IL-6 plays a unique role in initiating c-Maf expression during early stage of CD4 T cell activation. Yang, Y., Ochando, J., Yopp, A., Bromberg, J.S., Ding, Y. J. Immunol. (2005) [Pubmed]
  12. MafB, a new Maf family transcription activator that can associate with Maf and Fos but not with Jun. Kataoka, K., Fujiwara, K.T., Noda, M., Nishizawa, M. Mol. Cell. Biol. (1994) [Pubmed]
  13. Ecotropic C-type retrovirus of B16 melanoma and malignant transformation of normal melanocytes. Li, M., Xu, F., Muller, J., Hearing, V.J., Gorelik, E. Int. J. Cancer (1998) [Pubmed]
  14. Transcriptional regulation of mouse alphaB- and gammaF-crystallin genes in lens: opposite promoter-specific interactions between Pax6 and large Maf transcription factors. Yang, Y., Chauhan, B.K., Cveklova, K., Cvekl, A. J. Mol. Biol. (2004) [Pubmed]
  15. Repression of PML nuclear body-associated transcription by oxidative stress-activated Bach2. Tashiro, S., Muto, A., Tanimoto, K., Tsuchiya, H., Suzuki, H., Hoshino, H., Yoshida, M., Walter, J., Igarashi, K. Mol. Cell. Biol. (2004) [Pubmed]
  16. Members of the large Maf transcription family regulate insulin gene transcription in islet beta cells. Matsuoka, T.A., Zhao, L., Artner, I., Jarrett, H.W., Friedman, D., Means, A., Stein, R. Mol. Cell. Biol. (2003) [Pubmed]
  17. Oxidative stress abolishes leptomycin B-sensitive nuclear export of transcription repressor Bach2 that counteracts activation of Maf recognition element. Hoshino, H., Kobayashi, A., Yoshida, M., Kudo, N., Oyake, T., Motohashi, H., Hayashi, N., Yamamoto, M., Igarashi, K. J. Biol. Chem. (2000) [Pubmed]
  18. Differentially expressed Maf family transcription factors, c-Maf and MafA, activate glucagon and insulin gene expression in pancreatic islet alpha- and beta-cells. Kataoka, K., Shioda, S., Ando, K., Sakagami, K., Handa, H., Yasuda, K. J. Mol. Endocrinol. (2004) [Pubmed]
  19. Heme mediates derepression of Maf recognition element through direct binding to transcription repressor Bach1. Ogawa, K., Sun, J., Taketani, S., Nakajima, O., Nishitani, C., Sassa, S., Hayashi, N., Yamamoto, M., Shibahara, S., Fujita, H., Igarashi, K. EMBO J. (2001) [Pubmed]
  20. Regulation of c-maf gene expression by Pax6 in cultured cells. Sakai, M., Serria, M.S., Ikeda, H., Yoshida, K., Imaki, J., Nishi, S. Nucleic Acids Res. (2001) [Pubmed]
  21. The transcriptional programme of antibody class switching involves the repressor Bach2. Muto, A., Tashiro, S., Nakajima, O., Hoshino, H., Takahashi, S., Sakoda, E., Ikebe, D., Yamamoto, M., Igarashi, K. Nature (2004) [Pubmed]
  22. Impaired IL-4 production by CD8+ T cells in NOD mice is related to a defect of c-Maf binding to the IL-4 promoter. Chen, X.P., Falkner, D.H., Morel, P.A. Eur. J. Immunol. (2005) [Pubmed]
  23. Small Maf proteins serve as transcriptional cofactors for keratinocyte differentiation in the Keap1-Nrf2 regulatory pathway. Motohashi, H., Katsuoka, F., Engel, J.D., Yamamoto, M. Proc. Natl. Acad. Sci. U.S.A. (2004) [Pubmed]
  24. Regulation and differential expression of the c-maf gene in differentiating cultured cells. Serria, M.S., Ikeda, H., Omoteyama, K., Hirokawa, J., Nishi, S., Sakai, M. Biochem. Biophys. Res. Commun. (2003) [Pubmed]
  25. Impaired IL-4 and c-Maf expression and enhanced Th1-cell development in Vav1-deficient mice. Tanaka, Y., So, T., Lebedeva, S., Croft, M., Altman, A. Blood (2005) [Pubmed]
  26. Expression of the oxidative stress-regulated transcription factor bach2 in differentiating neuronal cells. Hoshino, H., Igarashi, K. J. Biochem. (2002) [Pubmed]
  27. Absence of transcription factor c-maf causes abnormal terminal differentiation of hypertrophic chondrocytes during endochondral bone development. MacLean, H.E., Kim, J.I., Glimcher, M.J., Wang, J., Kronenberg, H.M., Glimcher, L.H. Dev. Biol. (2003) [Pubmed]
  28. Requirement for the c-Maf transcription factor in crystallin gene regulation and lens development. Kim, J.I., Li, T., Ho, I.C., Grusby, M.J., Glimcher, L.H. Proc. Natl. Acad. Sci. U.S.A. (1999) [Pubmed]
  29. Tissue-specific regulation of the mouse alphaA-crystallin gene in lens via recruitment of Pax6 and c-Maf to its promoter. Yang, Y., Cvekl, A. J. Mol. Biol. (2005) [Pubmed]
  30. Hemoprotein Bach1 regulates enhancer availability of heme oxygenase-1 gene. Sun, J., Hoshino, H., Takaku, K., Nakajima, O., Muto, A., Suzuki, H., Tashiro, S., Takahashi, S., Shibahara, S., Alam, J., Taketo, M.M., Yamamoto, M., Igarashi, K. EMBO J. (2002) [Pubmed]
  31. Plasmacytic transcription factor blimp-1 is repressed by bach2 in B cells. Ochiai, K., Katoh, Y., Ikura, T., Hoshikawa, Y., Noda, T., Karasuyama, H., Tashiro, S., Muto, A., Igarashi, K. J. Biol. Chem. (2006) [Pubmed]
  32. Developmental contribution of c-maf in the kidney: distribution and developmental study of c-maf mRNA in normal mice kidney and histological study of c-maf knockout mice kidney and liver. Imaki, J., Tsuchiya, K., Mishima, T., Onodera, H., Kim, J.I., Yoshida, K., Ikeda, H., Sakai, M. Biochem. Biophys. Res. Commun. (2004) [Pubmed]
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