mafk transcription factor


Summary: A small Maf protein involved in differentiation of ERYTHROID CELLS. MafK was originally described as the small subunit of the NF-E2 Transcription Factor, but other small MAF PROTEINS also serve as NF-E2 subunits.

Top Publications

  1. Katsuoka F, Motohashi H, Tamagawa Y, Kure S, Igarashi K, Engel J, et al. Small Maf compound mutants display central nervous system neuronal degeneration, aberrant transcription, and Bach protein mislocalization coincident with myoclonus and abnormal startle response. Mol Cell Biol. 2003;23:1163-74 pubmed
    ..Thus compound mafG::mafK mutants develop age- and maf gene dosage-dependent cell-autonomous neuronal deficiencies that lead to profound neurological defects. ..
  2. Motohashi H, Igarashi K, Onodera K, Takahashi S, Ohtani H, Nakafuku M, et al. Mesodermal- vs. neuronal-specific expression of MafK is elicited by different promoters. Genes Cells. 1996;1:223-38 pubmed
  3. Suzuki H, Tashiro S, Hira S, Sun J, Yamazaki C, Zenke Y, et al. Heme regulates gene expression by triggering Crm1-dependent nuclear export of Bach1. EMBO J. 2004;23:2544-53 pubmed
    ..This region functioned as a heme-regulated NES dependent on the exporter Crm1. These results extend the regulatory roles for heme in protein sorting, and suggest that Bach1 transduces metabolic activity into gene expression. ..
  4. Nguyen T, Huang H, Pickett C. Transcriptional regulation of the antioxidant response element. Activation by Nrf2 and repression by MafK. J Biol Chem. 2000;275:15466-73 pubmed
    ..These data suggest that Nrf2 plays an important role mediating basal activity of the ARE but that small Maf proteins are repressors and not activators of ARE-mediated transcription. ..
  5. Katsuoka F, Motohashi H, Onodera K, Suwabe N, Engel J, Yamamoto M. One enhancer mediates mafK transcriptional activation in both hematopoietic and cardiac muscle cells. EMBO J. 2000;19:2980-91 pubmed
    ..These data provide the first in vivo demonstration that distinct members of a related transcription factor family activate the tissue-specific expression of a single target gene using the same cis-regulatory element. ..
  6. Dhakshinamoorthy S, Jaiswal A. Small maf (MafG and MafK) proteins negatively regulate antioxidant response element-mediated expression and antioxidant induction of the NAD(P)H:Quinone oxidoreductase1 gene. J Biol Chem. 2000;275:40134-41 pubmed
    ..In contrast to Maf-Nrf2, the Maf-Nrf1 heterodimers failed to bind with the NQO1 gene ARE and did not demonstrate the repressive effect in transfection assays. ..
  7. Ogawa K, Sun J, Taketani S, Nakajima O, Nishitani C, Sassa S, et al. Heme mediates derepression of Maf recognition element through direct binding to transcription repressor Bach1. EMBO J. 2001;20:2835-43 pubmed
    ..The repressor activity of Bach1 was lost upon addition of hemin in transfected cells. These results suggest that increased levels of heme inactivate the repressor Bach1, resulting in induction of a host of genes with MARES: ..
  8. Torocsik B, Angelastro J, Greene L. The basic region and leucine zipper transcription factor MafK is a new nerve growth factor-responsive immediate early gene that regulates neurite outgrowth. J Neurosci. 2002;22:8971-80 pubmed
    ..Our findings support a role for MafK as a novel regulator of neuronal differentiation. ..
  9. Oyake T, Itoh K, Motohashi H, Hayashi N, Hoshino H, Nishizawa M, et al. Bach proteins belong to a novel family of BTB-basic leucine zipper transcription factors that interact with MafK and regulate transcription through the NF-E2 site. Mol Cell Biol. 1996;16:6083-95 pubmed
    ..The results suggest that members of the Bach family play important roles in coordinating transcription activation and repression by MafK. ..

More Information


  1. Katsuoka F, Motohashi H, Ishii T, Aburatani H, Engel J, Yamamoto M. Genetic evidence that small maf proteins are essential for the activation of antioxidant response element-dependent genes. Mol Cell Biol. 2005;25:8044-51 pubmed
    ..These data explicitly demonstrate that small Mafs play critical roles in the inducible expression of a significant portion of ARE-dependent genes. ..
  2. Armstrong J, Emerson B. NF-E2 disrupts chromatin structure at human beta-globin locus control region hypersensitive site 2 in vitro. Mol Cell Biol. 1996;16:5634-44 pubmed
    ..Lastly, nucleosome disruption by NF-E2 is an ATP-dependent process, suggesting the involvement of energy-dependent nucleosome remodeling factors. ..
  3. Ohtsu H, Kuramasu A, Suzuki S, Igarashi K, Ohuchi Y, Sato M, et al. Histidine decarboxylase expression in mouse mast cell line P815 is induced by mouse peritoneal cavity incubation. J Biol Chem. 1996;271:28439-44 pubmed
    ..These results suggest that NF-E2 is also an important transcription factor in mast cell differentiation. ..
  4. Kotkow K, Orkin S. Complexity of the erythroid transcription factor NF-E2 as revealed by gene targeting of the mouse p18 NF-E2 locus. Proc Natl Acad Sci U S A. 1996;93:3514-8 pubmed
    ..We speculate that another member of the maf basic leucine zipper family substitutes for the p18 subunit in a complex with p45 NF-E2. Thus, p18 NF-E2 per se appears to be dispensable in vivo. ..
  5. Ney P, Andrews N, Jane S, Safer B, Purucker M, Weremowicz S, et al. Purification of the human NF-E2 complex: cDNA cloning of the hematopoietic cell-specific subunit and evidence for an associated partner. Mol Cell Biol. 1993;13:5604-12 pubmed
    ..Thus, p18 appears to be the sole specific partner of p45 NF-E2 in erythroid cells. Cloning of human p45 NF-E2 should permit studies of the role of NF-E2 in globin gene regulation and erythroid differentiation. ..
  6. Bulger M, Sawado T, Schübeler D, Groudine M. ChIPs of the beta-globin locus: unraveling gene regulation within an active domain. Curr Opin Genet Dev. 2002;12:170-7 pubmed
    ..Analysis of the effects of targeted deletion of the beta-globin LCR, along with emerging knowledge of the behavior of the erythroid transcription factor NF-E2, leads to a new perspective on factor binding and LCR function. ..
  7. Terui K, Takahashi Y, Kitazawa J, Toki T, Yokoyama M, Ito E. Expression of transcription factors during megakaryocytic differentiation of CD34+ cells from human cord blood induced by thrombopoietin. Tohoku J Exp Med. 2000;192:259-73 pubmed
    ..The dynamic changes in the levels of different transcription factors that occur during primary megakaryocytic differentiation suggest that the levels of these factors may influence the progression to specific hematopoietic pathways. ..
  8. Motohashi H, Katsuoka F, Shavit J, Engel J, Yamamoto M. Positive or negative MARE-dependent transcriptional regulation is determined by the abundance of small Maf proteins. Cell. 2000;103:865-75 pubmed
    ..These results provide direct in vivo evidence that transcriptional regulation through MARE elements hinges on an exquisitely sensitive balance of activating CNC molecules and their small Maf partners. ..
  9. Nanashima K, Mawatari T, Tahara N, Higuchi N, Nakaura A, Inamine T, et al. Genetic variants in antioxidant pathway: risk factors for hepatotoxicity in tuberculosis patients. Tuberculosis (Edinb). 2012;92:253-9 pubmed publisher
    ..Furthermore, a combination of BACH1 and MAFK polymorphisms may be useful as new biomarkers to identify high-risk Japanese TB patients for ATDH. ..
  10. Kotkow K, Orkin S. Dependence of globin gene expression in mouse erythroleukemia cells on the NF-E2 heterodimer. Mol Cell Biol. 1995;15:4640-7 pubmed
    ..From these results, we conclude that NF-E2 is specifically required for high level goblin gene expression in MEL cells. ..
  11. Ochiai K, Muto A, Tanaka H, Takahashi S, Igarashi K. Regulation of the plasma cell transcription factor Blimp-1 gene by Bach2 and Bcl6. Int Immunol. 2008;20:453-60 pubmed publisher
    ..Therefore, the interaction between Bach2 and Bcl6 might be crucial for the proper repression of Prdm1 in B cells. ..
  12. Murphy P, Kolstø A. Expression of the bZIP transcription factor TCF11 and its potential dimerization partners during development. Mech Dev. 2000;97:141-8 pubmed
    ..ATF4 shows evidence of complex regulation during development and shows elevated expression in many of the same sites as TCF11. ..
  13. Shimohata H, Yoh K, Fujita A, Morito N, Ojima M, Tanaka H, et al. MafA-deficient and beta cell-specific MafK-overexpressing hybrid transgenic mice develop human-like severe diabetic nephropathy. Biochem Biophys Res Commun. 2009;389:235-40 pubmed publisher
    ..MafA(-/-)MafK(+) mice might be a useful model for the analysis of human diabetic nephropathy. ..
  14. Okita Y, Kamoshida A, Suzuki H, Itoh K, Motohashi H, Igarashi K, et al. Transforming growth factor-? induces transcription factors MafK and Bach1 to suppress expression of the heme oxygenase-1 gene. J Biol Chem. 2013;288:20658-67 pubmed publisher
    ..As TGF-? is activated after tissue injury and in the process of cancer development, these findings suggest a novel mechanism by which damaged tissue becomes vulnerable to oxidative stress and xenobiotics. ..
  15. Francastel C, Augery Bourget Y, Prenant M, Walters M, Martin D, Robert Lézénès J. c-Jun inhibits NF-E2 transcriptional activity in association with p18/maf in Friend erythroleukemia cells. Oncogene. 1997;14:873-7 pubmed
    ..These results suggest that c-Jun could act as a repressor of NF-E2 transcriptional activity by forming inactive c-Jun/NF-E2p18 heterocomplexes which interfer with the transcription of globin genes in Friend erythroleukemia cells. ..
  16. Iwata T, Kogame K, Toki T, Yokoyama M, Yamamoto M, Ito E. Structure and chromosome mapping of the human small maf-genes MAFG and MAFK. Cytogenet Cell Genet. 1998;82:88-90 pubmed
    ..Human MAFG and MAFK are located at 17q25 and 7p22, respectively. Thus, small maf genes are not clustered in a single locus. ..
  17. Mosser E, Kasanov J, Forsberg E, Kay B, Ney P, Bresnick E. Physical and functional interactions between the transactivation domain of the hematopoietic transcription factor NF-E2 and WW domains. Biochemistry. 1998;37:13686-95 pubmed
    ..Mutation of PPXY-1, but not PPXY-2, inhibited the transactivation function of NF-E2, providing support for the hypothesis that WW domain interactions are important for NF-E2-mediated transactivation. ..
  18. Igarashi K, Kataoka K, Itoh K, Hayashi N, Nishizawa M, Yamamoto M. Regulation of transcription by dimerization of erythroid factor NF-E2 p45 with small Maf proteins. Nature. 1994;367:568-72 pubmed
  19. Meguro K, Igarashi K, Yamamoto M, Fujita H, Sassa S. The role of the erythroid-specific delta-aminolevulinate synthase gene expression in erythroid heme synthesis. Blood. 1995;86:940-8 pubmed
    ..These findings thus indicate that heme formation, which is determined by the level of ALAS-E, plays an essential role on gene expression of many proteins necessary for erythroid development. ..
  20. Ikeda H, Nishi S, Sakai M. Transcription factor Nrf2/MafK regulates rat placental glutathione S-transferase gene during hepatocarcinogenesis. Biochem J. 2004;380:515-21 pubmed
    ..These results indicate that the Nrf2/MafK heterodimer regulates GST-P gene expression during early hepatocarcinogenesis and in hepatoma cells...
  21. Lecoin L, Sii Felice K, Pouponnot C, Eychene A, Felder Schmittbuhl M. Comparison of maf gene expression patterns during chick embryo development. Gene Expr Patterns. 2004;4:35-46 pubmed
    ..mafA is found in the developing neural tube and dorsal root ganglia. c-maf hybridization is detected in the neuroretina, the notochord and the endothelium of extraembryonic blood vessels. ..
  22. Motohashi H. [Small Maf proteins as transcription factors regulating maturation and maintenance of the cell]. Seikagaku. 2003;75:1193-201 pubmed
  23. Tanito M, Masutani H, Kim Y, Nishikawa M, Ohira A, Yodoi J. Sulforaphane induces thioredoxin through the antioxidant-responsive element and attenuates retinal light damage in mice. Invest Ophthalmol Vis Sci. 2005;46:979-87 pubmed
    ..SF induced Trx in murine retina and effectively reduced retinal light damage. Evidence suggests that the ARE is involved in the mechanism of Trx induction by SF in RPE cells. ..
  24. Kim Y, Yamaguchi Y, Kondo N, Masutani H, Yodoi J. Thioredoxin-dependent redox regulation of the antioxidant responsive element (ARE) in electrophile response. Oncogene. 2003;22:1860-5 pubmed
    ..Therefore, ARE-mediated induction of thioredoxin expression is a mechanism of enhancing signal transduction through the ARE in electrophile-induced stress responses. ..
  25. Martínez Hernández A, Gutiérrez Malacatt H, Carrillo Sánchez K, Saldaña Alvarez Y, Rojas Ochoa A, Crespo Solís E, et al. Small MAF genes variants and chronic myeloid leukemia. Eur J Haematol. 2014;92:35-41 pubmed publisher
    ..After stratification by gender, the ACC and GTG haplotypes were associated only with males with CML. These novel data suggest an association between MAFF and MAFG and the development of CML. ..
  26. Moran J, Dahl E, Mulcahy R. Differential induction of mafF, mafG and mafK expression by electrophile-response-element activators. Biochem J. 2002;361:371-7 pubmed
  27. Igarashi K, Hoshino H, Muto A, Suwabe N, Nishikawa S, Nakauchi H, et al. Multivalent DNA binding complex generated by small Maf and Bach1 as a possible biochemical basis for beta-globin locus control region complex. J Biol Chem. 1998;273:11783-90 pubmed
  28. Shimohata H, Yoh K, Morito N, Shimano H, Kudo T, Takahashi S. MafK overexpression in pancreatic beta-cells caused impairment of glucose-stimulated insulin secretion. Biochem Biophys Res Commun. 2006;346:671-80 pubmed
    ..These results indicated that MafA may have relevance to compensatory response. ..
  29. Tanigawa S, Lee C, Lin C, Ku C, Hasegawa H, Qin S, et al. Jun dimerization protein 2 is a critical component of the Nrf2/MafK complex regulating the response to ROS homeostasis. Cell Death Dis. 2013;4:e921 pubmed publisher
    ..Taken together, these results suggest that JDP2 is an integral component of the Nrf2-MafK complex and that it modulates antioxidant and detoxification programs by acting via the ARE. ..
  30. Matsumoto M, Kondo K, Shiraki T, Brydun A, Funayama R, Nakayama K, et al. Genomewide approaches for BACH1 target genes in mouse embryonic fibroblasts showed BACH1-Pparg pathway in adipogenesis. Genes Cells. 2016;21:553-67 pubmed publisher
    ..Our results suggest that BACH1 regulates expression of adipocyte-related genes including Pparg and potentiates adipocyte differentiation capacity. ..
  31. Moroni E, Mastrangelo T, Razzini R, Cairns L, Moi P, Ottolenghi S, et al. Regulation of mouse p45 NF-E2 transcription by an erythroid-specific GATA-dependent intronic alternative promoter. J Biol Chem. 2000;275:10567-76 pubmed
    ..When the promoter 1b is placed 3' to the promoter 1a and reporter gene, in an arrangement that resembles the natural one, it acts as an enhancer to stimulate the activity of the upstream promoter la. ..
  32. Tian Y, Che F, Su Q, Lu Y, You C, Huang L, et al. Effects of mutant TDP-43 on the Nrf2/ARE pathway and protein expression of MafK and JDP2 in NSC-34 cells. Genet Mol Res. 2017;16: pubmed publisher
  33. Kobayashi A, Ito E, Toki T, Kogame K, Takahashi S, Igarashi K, et al. Molecular cloning and functional characterization of a new Cap'n' collar family transcription factor Nrf3. J Biol Chem. 1999;274:6443-52 pubmed
  34. Onishi Y, Kiyama R. Enhancer activity of HS2 of the human beta-LCR is modulated by distance from the key nucleosome. Nucleic Acids Res. 2001;29:3448-57 pubmed
    ..At this state, enhancer activity was approximately 50% of that in the original construct, presumably due to reduced binding of transcription factors. ..
  35. Martin F, van Deursen J, Shivdasani R, Jackson C, Troutman A, Ney P. Erythroid maturation and globin gene expression in mice with combined deficiency of NF-E2 and nrf-2. Blood. 1998;91:3459-66 pubmed
    ..Thus, the presence of a mild erythroid defect in NF-E2-deficient mice is not the result of compensation by Nrf-2. ..
  36. Blank V, Kim M, Andrews N. Human MafG is a functional partner for p45 NF-E2 in activating globin gene expression. Blood. 1997;89:3925-35 pubmed
    ..These results indicate that human MafG can serve as a functional partner for p45 NF-E2, and suggest that the p45/MafG heterodimer plays a role in the regulation of erythropoiesis. ..
  37. Ro Y, Jang B, Shin C, Park E, Kim C, Yang S. Akt regulates the expression of MafK, synaptotagmin I, and syntenin-1, which play roles in neuronal function. J Biomed Sci. 2010;17:18 pubmed publisher
    ..Taken together, these results indicate that Akt negatively regulates the expression of MafK, SytI, and Syn-1 genes that all participate in regulating neuronal integrity in some way or another. ..
  38. Onodera K, Shavit J, Motohashi H, Yamamoto M, Engel J. Perinatal synthetic lethality and hematopoietic defects in compound mafG::mafK mutant mice. EMBO J. 2000;19:1335-45 pubmed
    ..These data provide direct evidence that the small Maf transcription factors play an important regulatory role in erythropoiesis. ..
  39. Sekiguchi Y, Owada J, Oishi H, Katsumata T, Ikeda K, Kudo T, et al. Noninvasive monitoring of ?-cell mass and fetal ?-cell genesis in mice using bioluminescence imaging. Exp Anim. 2012;61:445-51 pubmed
    ..In summary, we show that bioluminescence imaging of mice expressing a ?-cell specific reporter allows detection of changes in ?-cell mass and visualization of fetal ?-cell neogenesis in uteri. ..
  40. Igarashi K, Itoh K, Motohashi H, Hayashi N, Matuzaki Y, Nakauchi H, et al. Activity and expression of murine small Maf family protein MafK. J Biol Chem. 1995;270:7615-24 pubmed
    ..mRNA for MafK is expressed in fractions enriched for hematopoietic stem cells as well as erythroid cells, suggesting that MafK plays an important regulatory role in hematopoiesis. ..
  41. Yamazaki H, Katsuoka F, Motohashi H, Engel J, Yamamoto M. Embryonic lethality and fetal liver apoptosis in mice lacking all three small Maf proteins. Mol Cell Biol. 2012;32:808-16 pubmed publisher
    ..These results thus demonstrate that small Maf proteins are indispensable for embryonic development after E9.5, especially for liver development, but early embryonic development does not require small Mafs. ..
  42. Yang H, Ko K, Xia M, Li T, Oh P, Li J, et al. Induction of avian musculoaponeurotic fibrosarcoma proteins by toxic bile acid inhibits expression of glutathione synthetic enzymes and contributes to cholestatic liver injury in mice. Hepatology. 2010;51:1291-301 pubmed publisher
    ..UDCA and SAMe treatment targets this switch. ..
  43. Motohashi H, Shavit J, Igarashi K, Yamamoto M, Engel J. The world according to Maf. Nucleic Acids Res. 1997;25:2953-59 pubmed
  44. Andrews N, Kotkow K, Ney P, Erdjument Bromage H, Tempst P, Orkin S. The ubiquitous subunit of erythroid transcription factor NF-E2 is a small basic-leucine zipper protein related to the v-maf oncogene. Proc Natl Acad Sci U S A. 1993;90:11488-92 pubmed
    ..It displays extensive homology to the v-maf oncogene product and a human retinal-specific protein, NRL. Unusual features in the basic region shared by v-Maf, NRL, and p18 place them in a distinct subfamily of AP-1-like proteins. ..
  45. Sakai M, Muramatsu M. Regulation of GST-P gene expression during hepatocarcinogenesis. Methods Enzymol. 2005;401:42-61 pubmed
  46. Brand M, Ranish J, Kummer N, Hamilton J, Igarashi K, Francastel C, et al. Dynamic changes in transcription factor complexes during erythroid differentiation revealed by quantitative proteomics. Nat Struct Mol Biol. 2004;11:73-80 pubmed
  47. Fujita A, Yoh K, Shimohata H, Morito N, Ojima M, Okamura M, et al. A novel diabetes mellitus mouse model, MAFA-deficient and beta cell-specific MAFK-overexpressing hybrid transgenic mice, developed severe diabetic nephropathy and improved with TCV-116 (candesartan cilexetil) treatment. Exp Anim. 2012;61:49-57 pubmed
    ..From these results, we concluded that the Mafa(-/-)Mafk (+) mouse is a useful model to analyze diabetic nephropathy and a useful tool for the development of new drugs to treat diabetic nephropathy. ..
  48. Ohta K, Ohigashi M, Naganawa A, Ikeda H, Sakai M, Nishikawa J, et al. Histone acetyltransferase MOZ acts as a co-activator of Nrf2-MafK and induces tumour marker gene expression during hepatocarcinogenesis. Biochem J. 2007;402:559-66 pubmed
    ..Further, exogenous MOZ induced GSTP expression in rat hepatoma H4IIE cells. These results suggest that during early hepatocarcinogenesis, aberrantly expressed MOZ may induce GSTP expression through the Nrf2-mediated pathway. ..
  49. Igarashi K, Katoh Y. Metabolic aspects of epigenome: coupling of S-adenosylmethionine synthesis and gene regulation on chromatin by SAMIT module. Subcell Biochem. 2013;61:105-18 pubmed publisher
    ..Considering their function, the heterooligomer of MATII? and ? is named SAMIT (SAM-integrating transcription) module within their interactome where it serves SAM for nuclear methyltransferases. ..
  50. Gong P, Stewart D, Hu B, Vinson C, Alam J. Multiple basic-leucine zipper proteins regulate induction of the mouse heme oxygenase-1 gene by arsenite. Arch Biochem Biophys. 2002;405:265-74 pubmed
    ..Together, these results implicate multiple basic-leucine zipper transcription factors in ho-1 gene activation by arsenite. ..
  51. Motohashi H, Katsuoka F, Miyoshi C, Uchimura Y, Saitoh H, Francastel C, et al. MafG sumoylation is required for active transcriptional repression. Mol Cell Biol. 2006;26:4652-63 pubmed
  52. Fujiwara K, Kataoka K, Nishizawa M. Two new members of the maf oncogene family, mafK and mafF, encode nuclear b-Zip proteins lacking putative trans-activator domain. Oncogene. 1993;8:2371-80 pubmed
    ..Tissue distributions of these three maf-family genes are different from one another, probably reflecting their different functions in vivo. ..
  53. Nioi P, McMahon M, Itoh K, Yamamoto M, Hayes J. Identification of a novel Nrf2-regulated antioxidant response element (ARE) in the mouse NAD(P)H:quinone oxidoreductase 1 gene: reassessment of the ARE consensus sequence. Biochem J. 2003;374:337-48 pubmed
    ..Furthermore, our results indicate that distinct AREs have differential sequence requirements, and a universally applicable consensus sequence cannot be derived. ..