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Gene Review

MAF  -  v-maf avian musculoaponeurotic...

Homo sapiens

Synonyms: CCA4, CTRCT21, Proto-oncogene c-Maf, Transcription factor Maf, V-maf musculoaponeurotic fibrosarcoma oncogene homolog, ...
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Disease relevance of MAF

  • C-MAF oncogene dysregulation in multiple myeloma: frequency and biological relevance [1].
  • Domain disruption and mutation of the bZIP transcription factor, MAF, associated with cataract, ocular anterior segment dysgenesis and coloboma [2].
  • Evidence for continuous basel generation of GC-MAF: absence in infantile osteopetrosis and restoration after bone marrow transplant [3].
  • The cataracts seen in Ofl heterozygotes and human MAF mutations are similar to one another, implying that Ofl may be a model of human pulverulent cortical cataract [4].
  • Monocytes were isolated and incubated for 24 hours in vitro with either medium (control), a crude mitogen-induced lymphokine preparation (MAF), or endotoxin before the addition of [125I]IUdR-labeled A375 melanoma target cells [5].

High impact information on MAF

  • Recombinant IFN gamma had potent MAF activity, stimulating the peroxide-releasing capacity of macrophages an average of 19.8-fold at peak response and enhancing their ability to kill toxoplasmas from 2.6 +/- 1.3% for untreated cells to 54 +/- 0.4% for treated cells [6].
  • Human blood mononuclear leukocytes stimulated with toxoplasma antigen, concanavalin A, mezerein plus lentil lectin, or staphylococcal enterotoxin A secreted a factor (macrophage-activating factor, or MAF) that enhanced the capacity of human macrophages to release H2O2 and to kill toxoplasmas [6].
  • Depletion of OKT4 antibody-binding cells abrogated the generation of MAF both by adult and cord blood MC [7].
  • Cloning the 16q23.2 breakpoint demonstrated that it transected the genomic-control domain of MAF, a basic region leucine zipper (bZIP) transcription factor, first identified as an oncogene, which is expressed in vertebrate lens development and regulates the expression of the eye lens crystallins [2].
  • The mutation results in the substitution of an evolutionarily highly conserved arginine with a proline at residue 288 (R288P) in the basic region of the DNA-binding domain of MAF [2].

Chemical compound and disease context of MAF


Biological context of MAF


Anatomical context of MAF

  • In this study, we show that the short form of the proto-oncogene c-maf, a known activator of the IL-4 gene, is highly induced in MCNS T cells during relapse, where it translocates to the nuclear compartment and binds to the DNA responsive element [15].
  • Here we analyzed the regulation of the human MAFF gene, coding for a small MAF transcription factor, in uterine smooth muscle cells [10].
  • Both proteins can be isolated from sponge cell membranes and from the sponge skeleton (insoluble extracellular matrix), but the 210-kDa MAF-binding protein can also be found in the soluble extracellular matrix (buffer washes of cells and skeleton) as well [16].
  • Finally, three antibodies with different specificities were found to abrogate the MAF and antiviral activities from lymphocyte culture supernatant [14].
  • All tumors contained at least focally an inactive embryonal epithelium identical morphologically to metanephric adenoma (MA), and hence each case could be classified as containing MAF [17].

Associations of MAF with chemical compounds

  • Generation of MAF by adult blood mononuclear cells was not inhibited by cord blood MC nor was generation of MAF by cord blood MC increased by depletion of OKT8 antibody-binding cells, by depletion of adherent cells with or without addition of adult adherent cells, or by addition of indomethacin [7].
  • Quantification of the amount of carbohydrate recovered in G-6 showed that one MAF molecule has about 950 repeats of this glycan [18].
  • Since the binding affinity of the T-10 glycopeptide fragment could be reconstituted by cross-linking, and since this fragment accounts for over 60% of MAF, we propose that the specificity and high affinity of the MAF-cell association is based on a highly polyvalent interaction of low affinity cell-binding sites [19].
  • Intermolecular cross-linking of the G-6 glycan with glutaraldehyde resulted, however, in the concomitant recovery of polyvalency (about 2200 repeats of G-6 per polymer of Mr greater than or equal to 1.5 x 10(7) and species-specific high cell binding affinity (K alpha = 1.6 x 10(9) M-1) but not of the MAF-MAF self-interaction activity [18].
  • By probing nitrocellulose blots of nonreducing sodium dodecyl sulfate gels containing whole sponge cell protein with iodinated MAF, a 210- and a 68-kDa protein, which have native molecular masses of approximately 200-400 and 70 kDa, were identified [16].

Physical interactions of MAF


Regulatory relationships of MAF

  • On the other hand, MAF was less effective in depressing antigen- and mitogen-induced proliferation of human blood cells than were NMS or human serum [20].

Other interactions of MAF

  • Our results suggest a possible specific role for MAFF in proinflammatory cytokine-mediated control of myometrial gene expression and provide the first link between a small MAF transcription factor and the inflammatory response [10].
  • The patterns of translocations and cyclin D expression (TC) define a novel classification that includes eight groups: 11q; 6p; MAF; 4p; D1 (34%); D1+D2 (6%); D2 (17%); and none (2%) [21].
  • Examination of the 248 bp AvrII-NheI fragment revealed the unexpected presence of three transcription factor binding sites (MAF/Ets, CTF/NF1 half site and ACAAAG enhancer) previously identified in the MMTV-LTR, and in WAP and milk gene promoters, proposed to mediate mammary-specific gene expression [22].
  • While these studies do not identify the inhibitory agent(s) present in MAF, they do suggest that mouse AFP either is pharmacologically different from human AFP and/or that the immunosuppressive activity attributed to mouse AFP is actually produced by another agent physically associated with it [20].
  • Comparison of published linkage and radiation hybrid (RH) maps of BTA18 with its evolutionary ortholog, human Chromosome (HSA) 16, revealed several potential candidate genes for the disorder including the MAF and FOXC 2 genes [23].

Analytical, diagnostic and therapeutic context of MAF


  1. C-MAF oncogene dysregulation in multiple myeloma: frequency and biological relevance. Rasmussen, T., Knudsen, L.M., Dahl, I.M., Johnsen, H.E. Leuk. Lymphoma (2003) [Pubmed]
  2. Domain disruption and mutation of the bZIP transcription factor, MAF, associated with cataract, ocular anterior segment dysgenesis and coloboma. Jamieson, R.V., Perveen, R., Kerr, B., Carette, M., Yardley, J., Heon, E., Wirth, M.G., van Heyningen, V., Donnai, D., Munier, F., Black, G.C. Hum. Mol. Genet. (2002) [Pubmed]
  3. Evidence for continuous basel generation of GC-MAF: absence in infantile osteopetrosis and restoration after bone marrow transplant. Datta, H.K., Cook, D.B., Kanan, R.M. Blood (1999) [Pubmed]
  4. 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]
  5. Activation of monocyte-mediated tumoricidal activity in patients with acquired immunodeficiency syndrome. Kleinerman, E.S., Ceccorulli, L.M., Zwelling, L.A., Twilley, T., Herberman, R.B., Jacob, J., Gelmann, E.P. J. Clin. Oncol. (1985) [Pubmed]
  6. Identification of interferon-gamma as the lymphokine that activates human macrophage oxidative metabolism and antimicrobial activity. Nathan, C.F., Murray, H.W., Wiebe, M.E., Rubin, B.Y. J. Exp. Med. (1983) [Pubmed]
  7. Cellular defenses against Toxoplasma gondii in newborns. Wilson, C.B., Haas, J.E. J. Clin. Invest. (1984) [Pubmed]
  8. Triple drug chemotherapy for advanced ovarian carcinoma: comparative study of two regimens. Aroney, R.S., Levi, J.A., Dalley, D.N. Med. J. Aust. (1981) [Pubmed]
  9. Epidemiologic survey on organophosphate-induced delayed polyneuropathy (OPIDP) among patients recovered from Methamidophos poisoning. Sun, D.H., Zhou, H.D., Xue, S.Z. La Medicina del lavoro. (1998) [Pubmed]
  10. Regulation of the MAFF transcription factor by proinflammatory cytokines in myometrial cells. Massrieh, W., Derjuga, A., Doualla-Bell, F., Ku, C.Y., Sanborn, B.M., Blank, V. Biol. Reprod. (2006) [Pubmed]
  11. A mammary cell-specific enhancer in mouse mammary tumor virus DNA is composed of multiple regulatory elements including binding sites for CTF/NFI and a novel transcription factor, mammary cell-activating factor. Mink, S., Härtig, E., Jennewein, P., Doppler, W., Cato, A.C. Mol. Cell. Biol. (1992) [Pubmed]
  12. Virally mediated MafB transduction induces the monocyte commitment of human CD34+ hematopoietic stem/progenitor cells. Gemelli, C., Montanari, M., Tenedini, E., Zanocco Marani, T., Vignudelli, T., Siena, M., Zini, R., Salati, S., Tagliafico, E., Manfredini, R., Grande, A., Ferrari, S. Cell Death Differ. (2006) [Pubmed]
  13. Cytolytic interactions between murine macrophages, tumor cells, and monoclonal antibodies: characterization of lytic conditions and requirements for effector activation. Johnson, W.J., Steplewski, Z., Matthews, T.J., Hamilton, T.A., Koprowski, H., Adams, D.O. J. Immunol. (1986) [Pubmed]
  14. Identity between human interferon-gamma and "macrophage-activating factor" produced by human T lymphocytes. Talmadge, K.W., Gallati, H., Sinigaglia, F., Walz, A., Garotta, G. Eur. J. Immunol. (1986) [Pubmed]
  15. NF-kappa B p65 antagonizes IL-4 induction by c-maf in minimal change nephrotic syndrome. Valanciuté, A., le Gouvello, S., Solhonne, B., Pawlak, A., Grimbert, P., Lyonnet, L., Hue, S., Lang, P., Remy, P., Salomon, R., Bensman, A., Guellaën, G., Sahali, D. J. Immunol. (2004) [Pubmed]
  16. Two cell surface proteins bind the sponge Microciona prolifera aggregation factor. Varner, J.A., Burger, M.M., Kaufman, J.F. J. Biol. Chem. (1988) [Pubmed]
  17. The spectrum of metanephric adenofibroma and related lesions: clinicopathologic study of 25 cases from the National Wilms Tumor Study Group Pathology Center. Arroyo, M.R., Green, D.M., Perlman, E.J., Beckwith, J.B., Argani, P. Am. J. Surg. Pathol. (2001) [Pubmed]
  18. The species-specific cell-binding site of the aggregation factor from the sponge Microciona prolifera is a highly repetitive novel glycan containing glucuronic acid, fucose, and mannose. Misevic, G.N., Burger, M.M. J. Biol. Chem. (1990) [Pubmed]
  19. Reconstitution of high cell binding affinity of a marine sponge aggregation factor by cross-linking of small low affinity fragments into a large polyvalent polymer. Misevic, G.N., Burger, M.M. J. Biol. Chem. (1986) [Pubmed]
  20. Immunosuppressive properties of mouse amniotic fluid. Tyan, M.L. Proc. Soc. Exp. Biol. Med. (1976) [Pubmed]
  21. Molecular pathogenesis and a consequent classification of multiple myeloma. Bergsagel, P.L., Kuehl, W.M. J. Clin. Oncol. (2005) [Pubmed]
  22. MMTV-associated transcription factor binding sites increase nm23-H1 metastasis suppressor gene expression in human breast carcinoma cell lines. Ouatas, T., Clare, S.E., Hartsough, M.T., De La Rosa, A., Steeg, P.S. Clin. Exp. Metastasis (2002) [Pubmed]
  23. Linkage mapping of the locus responsible for congenital multiple ocular defects in cattle on bovine Chromosome 18. Abbasi, A.R., Ihara, N., Watanabe, T., Khalaj, M., Tsuji, T., Sugimoto, Y., Kunieda, T. Mamm. Genome (2005) [Pubmed]
  24. Atrial electrophysiologic abnormalities in patients with Wolff-Parkinson-White syndrome but without paroxysmal atrial fibrillation. Sakabe, K., Fukuda, N., Nada, T., Shinohara, H., Tamura, Y., Wakatsuki, T., Nishikado, A., Oki, T. Clinical cardiology. (2004) [Pubmed]
  25. Diagnostic signs of accommodative insufficiency. Cacho, P., García, A., Lara, F., Seguí, M.M. Optometry and vision science : official publication of the American Academy of Optometry. (2002) [Pubmed]
  26. Mango seed uses: thermal behaviour of mango seed almond fat and its mixtures with cocoa butter. Solís-Fuentes, J.A., Durán-de-Bazúa, M.C. Bioresour. Technol. (2004) [Pubmed]
  27. Purification and sequencing of glycosylation variants of BSF-1, as a MAF, from the EL-4 leukaemia cell line. Sutton, C., Depledge, P., Bawden, L., Carne, A., Meltzer, M., Newton, V., Vodinelich, L. Journal of biological standardization. (1989) [Pubmed]
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