mafb transcription factor


Summary: A large maf protein that regulates HINDBRAIN development, contributes to CELL DIFFERENTIATION of MONOCYTES, and interacts with ETS-1 TRANSCRIPTION FACTOR.

Top Publications

  1. Machiya J, Shibata Y, Yamauchi K, Hirama N, Wada T, Inoue S, et al. Enhanced expression of MafB inhibits macrophage apoptosis induced by cigarette smoke exposure. Am J Respir Cell Mol Biol. 2007;36:418-26 pubmed
    ..These results suggest that enhanced MafB expression by oxidative stress inhibits AM cell death and prolongs their survival in the CS-exposed lung. ..
  2. Kim K, Kim J, Lee J, Jin H, Kook H, Kim K, et al. MafB negatively regulates RANKL-mediated osteoclast differentiation. Blood. 2007;109:3253-9 pubmed
    ..Taken together, our results suggest that MafB can act as an important modulator of RANKL-mediated osteoclastogenesis. ..
  3. Van Stralen E, van de Wetering M, Agnelli L, Neri A, Clevers H, Bast B. Identification of primary MAFB target genes in multiple myeloma. Exp Hematol. 2009;37:78-86 pubmed publisher
    ..Eleven of these genes are novel in the C-MAF pathway as well. These direct target genes may be responsible for the oncogenic transformation of MAF expressing myeloma cells. ..
  4. Sadl V, Jin F, Yu J, Cui S, Holmyard D, Quaggin S, et al. The mouse Kreisler (Krml1/MafB) segmentation gene is required for differentiation of glomerular visceral epithelial cells. Dev Biol. 2002;249:16-29 pubmed
    ..However, these observations alone are unlikely to account for the aberrant podocyte foot process formation. Thus, Kreisler must regulate other unknown genes required for podocyte function and with possible roles in kidney disease. ..
  5. Gemelli C, Montanari M, Tenedini E, Zanocco Marani T, Vignudelli T, Siena M, et al. Virally mediated MafB transduction induces the monocyte commitment of human CD34+ hematopoietic stem/progenitor cells. Cell Death Differ. 2006;13:1686-96 pubmed
    ..Although MafB transcription factor is believed to play a role in the regulation of monocytic commitment, no demonstration is, to date, ..
  6. Zhao L, Guo M, Matsuoka T, Hagman D, Parazzoli S, Poitout V, et al. The islet beta cell-enriched MafA activator is a key regulator of insulin gene transcription. J Biol Chem. 2005;280:11887-94 pubmed
    ..Collectively, these results suggest that MafA plays a key role in coordinating and controlling the level of insulin gene expression in islet beta cells. ..
  7. Blanchi B, Kelly L, Viemari J, Lafon I, Burnet H, Bevengut M, et al. MafB deficiency causes defective respiratory rhythmogenesis and fatal central apnea at birth. Nat Neurosci. 2003;6:1091-100 pubmed
    ..Our results show an essential role of MafB in central respiratory control, possibly involving the specification of rhythmogenic preBötC neurons. ..
  8. Matsuoka T, Zhao L, Artner I, Jarrett H, Friedman D, Means A, et al. Members of the large Maf transcription family regulate insulin gene transcription in islet beta cells. Mol Cell Biol. 2003;23:6049-62 pubmed
    ..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. ..
  9. Tillmanns S, Otto C, Jaffray E, Du Roure C, Bakri Y, Vanhille L, et al. SUMO modification regulates MafB-driven macrophage differentiation by enabling Myb-dependent transcriptional repression. Mol Cell Biol. 2007;27:5554-64 pubmed
    ..SUMO modification of lineage-specific transcription factors may thus modulate transcription factor antagonism to control tissue homeostasis in the hematopoietic system. ..

More Information


  1. Nishimura W, Rowan S, Salameh T, Maas R, Bonner Weir S, Sell S, et al. Preferential reduction of beta cells derived from Pax6-MafB pathway in MafB deficient mice. Dev Biol. 2008;314:443-56 pubmed publisher
    ..Thus, Pax6 acts upstream of MafB, which in turn may trigger the expression of insulin and regulate the PDX-1 and MafA expression required for beta-cell maturation. ..
  2. Artner I, Hang Y, Guo M, Gu G, Stein R. MafA is a dedicated activator of the insulin gene in vivo. J Endocrinol. 2008;198:271-9 pubmed publisher
    ..Collectively, these results demonstrate a unique ability for MafA to independently activate Insulin transcription. ..
  3. Huang K, Serria M, Nakabayashi H, Nishi S, Sakai M. Molecular cloning and functional characterization of the mouse mafB gene. Gene. 2000;242:419-26 pubmed
    ..In addition, cotransfection analysis indicated that the MyoD activates the mouse mafB promoter and the gene is positively auto-regulated by its own product. ..
  4. Wang P, Eisenbart J, Cordes S, Barsh G, Stoffel M, Le Beau M. Human KRML (MAFB): cDNA cloning, genomic structure, and evaluation as a candidate tumor suppressor gene in myeloid leukemias. Genomics. 1999;59:275-81 pubmed
    ..Thus, KRML is unlikely to be involved in the pathogenesis of malignant myeloid disorders characterized by abnormalities of chromosome 20. ..
  5. Sato M, Shibata Y, Kimura T, Yamauchi K, Abe S, Inoue S, et al. Immunohistochemical staining for transcription factor MafB in alveolar macrophages is correlated with spirometric measures of airflow limitation in smokers. Respirology. 2011;16:124-30 pubmed publisher
    ..The degree of immunostaining for MafB in AM was correlated with the degree of AFL in smokers. MafB may be involved in the pathophysiology of COPD. ..
  6. Cordes S, Barsh G. The mouse segmentation gene kr encodes a novel basic domain-leucine zipper transcription factor. Cell. 1994;79:1025-34 pubmed
    ..The identity, expression, and mutant phenotype of kr indicate an early role in axial patterning and provide insights into the molecular and embryologic mechanisms that govern hindbrain and otic development. ..
  7. Artner I, Blanchi B, Raum J, Guo M, Kaneko T, Cordes S, et al. MafB is required for islet beta cell maturation. Proc Natl Acad Sci U S A. 2007;104:3853-8 pubmed
    ..These results demonstrate that MafB plays a previously uncharacterized role by regulating transcription of key factors during development that are required for the production of mature alpha and beta cells. ..
  8. Sarrazin S, Mossadegh Keller N, Fukao T, Aziz A, Mourcin F, Vanhille L, et al. MafB restricts M-CSF-dependent myeloid commitment divisions of hematopoietic stem cells. Cell. 2009;138:300-13 pubmed publisher
    ..Together, this indicates that an integrated transcription factor/cytokine circuit can control the rate of specific HSC commitment divisions without compromising other lineages or self-renewal. ..
  9. Artner I, Hang Y, Mazur M, Yamamoto T, Guo M, Lindner J, et al. MafA and MafB regulate genes critical to beta-cells in a unique temporal manner. Diabetes. 2010;59:2530-9 pubmed publisher
    ..Our results provide insight into the sequential manner by which MafA and MafB regulate islet ?-cell formation and maturation. ..
  10. Aziz A, Vanhille L, Mohideen P, Kelly L, Otto C, Bakri Y, et al. Development of macrophages with altered actin organization in the absence of MafB. Mol Cell Biol. 2006;26:6808-18 pubmed
    ..Together these data point to an unexpected redundancy of MafB function in macrophage differentiation and a previously unknown role in actin-dependent macrophage morphology. ..
  11. Moriguchi T, Hamada M, Morito N, Terunuma T, Hasegawa K, Zhang C, et al. MafB is essential for renal development and F4/80 expression in macrophages. Mol Cell Biol. 2006;26:5715-27 pubmed
    ..These results demonstrate that MafB is essential for podocyte differentiation, renal tubule survival, and F4/80 maturation in a distinct subpopulation of nonadherent mature macrophages. ..
  12. Nishimura W, Kondo T, Salameh T, El Khattabi I, Dodge R, Bonner Weir S, et al. A switch from MafB to MafA expression accompanies differentiation to pancreatic beta-cells. Dev Biol. 2006;293:526-39 pubmed
    ..Thus, this redundancy in the function and expression of the large-Maf factors may explain the normal islet morphology observed in the MafA knockout mice at birth. ..
  13. Howell K, Posluszny J, He L, Szilagyi A, Halerz J, Gamelli R, et al. High MafB expression following burn augments monocyte commitment and inhibits DC differentiation in hemopoietic progenitors. J Leukoc Biol. 2012;91:69-81 pubmed publisher
    ..We provide evidence that high MafB following burn plays an inhibitory role in monocyte-derived DC differentiation by regulating M-CSFR and GATA-1 expressions. ..
  14. Sieweke M, Tekotte H, Frampton J, Graf T. MafB is an interaction partner and repressor of Ets-1 that inhibits erythroid differentiation. Cell. 1996;85:49-60 pubmed
    ..These results highlight the importance of inhibitory interactions between transcription factors in regulating lineage-specific gene expression. ..
  15. Ogata A, Shimizu T, Abe R, Shimizu H, Sakai M. Expression of c-maf and mafB genes in the skin during rat embryonic development. Acta Histochem. 2004;106:65-7 pubmed
    ..MafB showed similar expression patterns as c-maf. Our findings indicate that c-maf and mafB are involved in embryonic development of epidermis and hair follicles. ..
  16. Nishizawa M, Kataoka K, Vogt P. MafA has strong cell transforming ability but is a weak transactivator. Oncogene. 2003;22:7882-90 pubmed
    ..These regulatable constructs permit a kinetic characterization of target gene responses and facilitate discrimination between direct and indirect targets. ..
  17. Artner I, Le Lay J, Hang Y, Elghazi L, Schisler J, Henderson E, et al. MafB: an activator of the glucagon gene expressed in developing islet alpha- and beta-cells. Diabetes. 2006;55:297-304 pubmed
    ..These results indicate that MafB is not only important to islet alpha-cell function but may also be involved in regulating genes required in both endocrine alpha- and beta-cell differentiation. ..
  18. Kataoka K, Fujiwara K, Noda M, Nishizawa M. MafB, a new Maf family transcription activator that can associate with Maf and Fos but not with Jun. Mol Cell Biol. 1994;14:7581-91 pubmed
    ..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. ..
  19. Kanai K, Reza H, Kamitani A, Hamazaki Y, Han S, Yasuda K, et al. SUMOylation negatively regulates transcriptional and oncogenic activities of MafA. Genes Cells. 2010;15:971-82 pubmed publisher
    ..Therefore, SUMOylation is a functional post-translational modification of MafA that negatively regulates its transcriptional and transforming activities. ..
  20. Waqas S, Hoang A, Lin Y, Ampem G, Azegrouz H, Balogh L, et al. Neuropeptide FF increases M2 activation and self-renewal of adipose tissue macrophages. J Clin Invest. 2017;127:2842-2854 pubmed publisher
    ..NPFF thus plays an important role in supporting healthy adipose tissue via the maintenance of metabolically beneficial ATMs. ..
  21. Beaty T, Murray J, Marazita M, Munger R, Ruczinski I, Hetmanski J, et al. A genome-wide association study of cleft lip with and without cleft palate identifies risk variants near MAFB and ABCA4. Nat Genet. 2010;42:525-9 pubmed publisher
    ..Expression studies support a role for MAFB in palatal development...
  22. Shichita T, Ito M, Morita R, Komai K, Noguchi Y, Ooboshi H, et al. MAFB prevents excess inflammation after ischemic stroke by accelerating clearance of damage signals through MSR1. Nat Med. 2017;23:723-732 pubmed publisher
    ..Our findings uncover cellular mechanisms contributing to DAMP clearance in resolution of the sterile inflammation triggered by tissue injury. ..
  23. Medina A, Yamada S, Hara A, Hamamoto K, Kojima I. Involvement of the parasympathetic nervous system in the initiation of regeneration of pancreatic ?-cells. Endocr J. 2013;60:687-96 pubmed
    ..These results strongly suggest that the vagal nerve is involved in ?-cell proliferation, induction of endocrine progenitors and neogenesis of ?- and ?-cells. ..
  24. Fan L, Shen J. [Expression of Maf-b mRNA in de novo leukemia patients and its clinical significance]. Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2010;18:1147-50 pubmed
    ..01). It is concluded that there is low expression of maf-b gene in AML patients. Abnormal expression of maf-b correlates with abnormal proliferation of AML cells, which may be a new prognostic factor for AML. ..
  25. Manzanares M, Cordes S, Kwan C, Sham M, Barsh G, Krumlauf R. Segmental regulation of Hoxb-3 by kreisler. Nature. 1997;387:191-5 pubmed
    ..These studies demonstrate that Krml1 directly activates expression of Hoxb-3 in r5 in combination with an Ets-related activation site, and suggest that kreisler plays a primary role in regulating segmental identity through Hox genes. ..
  26. Aziz A, Soucie E, Sarrazin S, Sieweke M. MafB/c-Maf deficiency enables self-renewal of differentiated functional macrophages. Science. 2009;326:867-71 pubmed publisher
    ..It thus appears possible to amplify functional differentiated cells without malignant transformation or stem cell intermediates. ..
  27. Sing A, Pannell D, Karaiskakis A, Sturgeon K, Djabali M, Ellis J, et al. A vertebrate Polycomb response element governs segmentation of the posterior hindbrain. Cell. 2009;138:885-97 pubmed publisher
    ..Thus, we provide evidence that similar to invertebrates, PREs act as entry sites for PcG/trxG chromatin remodeling in vertebrates. ..
  28. Sultana D, Tomita S, Hamada M, Iwanaga Y, Kitahama Y, Khang N, et al. Gene expression profile of the third pharyngeal pouch reveals role of mesenchymal MafB in embryonic thymus development. Blood. 2009;113:2976-87 pubmed publisher
    ..These results suggest that MafB expressed in third pharyngeal pouch mesenchymal cells critically regulates lymphocyte accumulation in the embryonic thymus. ..
  29. Cooke J, Moens C, Roth L, Durbin L, Shiomi K, Brennan C, et al. Eph signalling functions downstream of Val to regulate cell sorting and boundary formation in the caudal hindbrain. Development. 2001;128:571-80 pubmed
    ..We propose that Val controls eph expression and that interactions between EphB4a and Ephrin-B2a mediate cell sorting and boundary formation in the segmenting caudal hindbrain. ..
  30. Kayam G, Kohl A, Magen Z, Peretz Y, Weisinger K, Bar A, et al. A novel role for Pax6 in the segmental organization of the hindbrain. Development. 2013;140:2190-202 pubmed publisher
    ..This study unravels a novel role for Pax6 in the segmental organization of the early hindbrain and provides new evidence for its significance in regional organization along the central nervous system...
  31. Sato Nishiwaki M, Aida Y, Abe S, Shibata Y, Kimura T, Yamauchi K, et al. Reduced number and morphofunctional change of alveolar macrophages in MafB gene-targeted mice. PLoS ONE. 2013;8:e73963 pubmed publisher
    ..MSR-DN MafB TG mice may present a useful model to clarify the precise role of MafB in macrophages. ..
  32. Barisoni L, Nelson P. Collapsing glomerulopathy: an inflammatory podocytopathy?. Curr Opin Nephrol Hypertens. 2007;16:192-5 pubmed
    ..This may manifest as collapsing glomerulopathy or crescentic glomerulonephritis--lesions that appear to be anatomically and pathogenically linked. ..
  33. Petersen H, Hilpert J, Jacobsen C, Lauwers A, Roebroek A, Willnow T. Low-density lipoprotein receptor-related protein interacts with MafB, a regulator of hindbrain development. FEBS Lett. 2004;565:23-7 pubmed
    ..The ICD co-localizes with MafB to the nucleus and negatively regulates its transcriptional activity, suggesting a possible role for LRP in brain development. ..
  34. Lian X, Yan C, Qin Y, Knox L, Li T, Du H. Neutral lipids and peroxisome proliferator-activated receptor-{gamma} control pulmonary gene expression and inflammation-triggered pathogenesis in lysosomal acid lipase knockout mice. Am J Pathol. 2005;167:813-21 pubmed
    ..These data suggest that inflammation-triggered cell growth and emphysema during lysosomal acid lipase deficiency are partially caused by peroxisome proliferator-activated receptor-gamma inactivation. ..
  35. Goudot C, Coillard A, Villani A, Guéguen P, Cros A, Sarkizova S, et al. Aryl Hydrocarbon Receptor Controls Monocyte Differentiation into Dendritic Cells versus Macrophages. Immunity. 2017;47:582-596.e6 pubmed publisher
    ..These results establish that mo-DCs and mo-Macs are controlled by distinct transcription factors and show that AHR acts as a molecular switch for monocyte fate specification in response to micro-environmental factors. ..
  36. Williams K, Szilagyi A, He L, Conrad P, Halerz M, Gamelli R, et al. Dendritic cell depletion in burn patients is regulated by MafB expression. J Burn Care Res. 2012;33:747-58 pubmed publisher
    ..This impairment is likely secondary to the down-regulation of mDC differentiation by high MafB-expressing monocytes following burn injury. ..
  37. Morita M, Nakamura M, Hamada M, Takahashi S. Combinatorial motif analysis of regulatory gene expression in Mafb deficient macrophages. BMC Syst Biol. 2011;5 Suppl 2:S7 pubmed publisher
    ..In addition, these findings show that analysis of combinations of evolutionarily conserved motifs can be successfully used to identify patterns of gene regulation. ..
  38. Potapova A, Hasemeier B, Römermann D, Metzig K, Göhring G, Schlegelberger B, et al. Epigenetic inactivation of tumour suppressor gene KLF11 in myelodysplastic syndromes*. Eur J Haematol. 2010;84:298-303 pubmed publisher
    ..05). In conclusion, epigenetic inactivation and subsequent transcriptional repression of the KLF11 gene is quite frequent in MDS. Patients with an isolated 5q-deletion seem to harbour a distinct epigenetic profile. ..
  39. Lazarus S, Tseng H, Lawrence F, Woodruff M, Duncan E, Pettit A. Characterization of Normal Murine Carpal Bone Development Prompts Re-Evaluation of Pathologic Osteolysis as the Cause of Human Carpal-Tarsal Osteolysis Disorders. Am J Pathol. 2017;187:1923-1934 pubmed publisher
    ..Thus, abnormal peri-articular skeletal development and modeling, rather than excessive bone resorption, may be the underlying pathophysiology of these skeletal syndromes. ..
  40. Pechhold S, Stouffer M, Walker G, Martel R, Seligmann B, Hang Y, et al. Transcriptional analysis of intracytoplasmically stained, FACS-purified cells by high-throughput, quantitative nuclease protection. Nat Biotechnol. 2009;27:1038-42 pubmed publisher
    ..Application of qNPA to intracellularly stained, FACS-sorted cells should be broadly applicable to the analysis of gene expression in subpopulations of any heterogeneous tissue, including tumors. ..
  41. Manzanares M, Trainor P, Nonchev S, Ariza McNaughton L, Brodie J, Gould A, et al. The role of kreisler in segmentation during hindbrain development. Dev Biol. 1999;211:220-37 pubmed
    ..We conclude that the mouse kreisler gene regulates multiple steps in segmental patterning involving both the formation of segments and their A-P identity. ..
  42. Pouilhe M, Gilardi Hebenstreit P, Desmarquet Trin Dinh C, Charnay P. Direct regulation of vHnf1 by retinoic acid signaling and MAF-related factors in the neural tube. Dev Biol. 2007;309:344-57 pubmed
    ..We propose a model accounting for the initiation and maintenance phases of vHnf1 expression and for the establishment of the r4/r5 boundary, based on cooperative contributions of Maf factors and retinoic acid signaling. ..
  43. Chatonnet F, del Toro E, Voiculescu O, Charnay P, Champagnat J. Different respiratory control systems are affected in homozygous and heterozygous kreisler mutant mice. Eur J Neurosci. 2002;15:684-92 pubmed
    ..A different rhythm-promoting system originates in r5 and kreisler controls the development of antiapneic and chemosensory signal transmission at this level. ..
  44. Hashizume H, Hamalainen H, Sun Q, Sucharczuk A, Lahesmaa R. Downregulation of mafB expression in T-helper cells during early differentiation in vitro. Scand J Immunol. 2003;57:28-34 pubmed
  45. Kim F, Sing l A, Kaneko T, Bieman M, Stallwood N, Sadl V, et al. The vHNF1 homeodomain protein establishes early rhombomere identity by direct regulation of Kreisler expression. Mech Dev. 2005;122:1300-9 pubmed
  46. Choe S, Zhang X, Hirsch N, Straubhaar J, SAGERSTROM C. A screen for hoxb1-regulated genes identifies ppp1r14al as a regulator of the rhombomere 4 Fgf-signaling center. Dev Biol. 2011;358:356-67 pubmed publisher
    ..Furthermore, ppp1r14al is essential for establishment of the earliest hindbrain signaling-center in rhombomere 4 by regulating expression of fgf3. ..
  47. Stanley E. Lineage commitment: cytokines instruct, at last!. Cell Stem Cell. 2009;5:234-6 pubmed publisher
    ..Instructive and permissive models of commitment have been proposed for hematopoietic cytokines. In recent issues of Science and Cell, Rieger et al. (2009) and Sarrazin et al. (2009) together show that cytokines can instruct lineage choice. ..
  48. Niederreither K, Vermot J, Schuhbaur B, Chambon P, Dolle P. Retinoic acid synthesis and hindbrain patterning in the mouse embryo. Development. 2000;127:75-85 pubmed
    ..We conclude that RA produced by the embryo is required to generate posterior cell fates in the developing mouse hindbrain, its absence leading to an abnormal r3 (and, to a lesser extent, r4) identity of the caudal hindbrain cells. ..
  49. Wendling O, Ghyselinck N, Chambon P, Mark M. Roles of retinoic acid receptors in early embryonic morphogenesis and hindbrain patterning. Development. 2001;128:2031-8 pubmed
  50. Xiu F, Stanojcic M, Jeschke M. Norepinephrine inhibits macrophage migration by decreasing CCR2 expression. PLoS ONE. 2013;8:e69167 pubmed publisher
    ..Our results demonstrate that NE regulates macrophage differentiation, proliferation and function, and may play a critical role in the dysfunctional immune response post-burn. ..
  51. Martens G, Motte E, Kramer G, Stange G, Gaarn L, Hellemans K, et al. Functional characteristics of neonatal rat ? cells with distinct markers. J Mol Endocrinol. 2014;52:11-28 pubmed publisher
  52. Gemelli C, Zanocco Marani T, Bicciato S, Mazza E, Boraschi D, Salsi V, et al. MafB is a downstream target of the IL-10/STAT3 signaling pathway, involved in the regulation of macrophage de-activation. Biochim Biophys Acta. 2014;1843:955-64 pubmed publisher
    In spite of the numerous reports implicating MafB transcription factor in the molecular control of monocyte-macrophage differentiation, the precise genetic program underlying this activity has been, to date, poorly understood...
  53. Imaki J, Onodera H, Mishima T, Yoshida K, Sakai M. Developmental expression of mafB messenger ribonucleic acids in rat skin by in situ hybridization histochemistry. J Dermatol Sci. 2003;33:134-6 pubmed