Differentially expressed Maf family transcription factors, c-Maf and MafA, activate glucagon and insulin gene expression in pancreatic islet alpha- and beta-cells

Kataoka, Kohsuke; Shioda, Shigeo; Ando, Kozue; Sakagami, Kiyo; Handa, Hiroshi; Yasuda, Kazuaki

doi:10.1677/jme.0.0320009

Cited by 78 publications

(63 citation statements)

References 45 publications

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“…Moreover, the highest activation potential of MafA was found among other insulin regulatory factors. 47 It is important to note that other tissue-restricted genes including BETA-2/NeuroD, Cdx2/3, Nkx2.2 and Pdx-1 are involved in the regulation of these genes in pancreas. 48 In corneal epithelium, Pax6 functionally interacts with AP-2α to regulate expression of gelatinase B/MMP9.…”

Section: Discussionmentioning

confidence: 99%

Tissue-specific Regulation of the Mouse αA-crystallin Gene in Lens via Recruitment of Pax6 and c-Maf to its Promoter

Yang

Cvekl

2005

Journal of Molecular Biology

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Pax6 is a lineage-restricted DNA-binding transcription factor regulating the formation of mammalian organs including brain, eye and pancreas. Pax6 plays key roles during the initial formation of lens lineage, proliferation of lens progenitor and precursor cells and their terminal differentiation. In addition to Pax6, lens fiber cell differentiation is regulated by c-Maf, Prox1 and Sox1. Crystallins are essential lens structural proteins required for light refraction and transparency. Mouse αA-crystallin represents about 17% of all crystallins at the protein level and ranks as one of the most abundant tissue-specific proteins. Lens-specific expression of this gene is regulated at the level of transcription. A promoter fragment of −88 to +46 is capable of driving lens-specific expression in transgenic mouse. Here we provide data suggesting that this lens-specific promoter fragment is comprised of multiple Pax6 and Maf-binding sites. Site-directed mutagenesis of regions within these sites resulted in partially or completely reduced promoter activities in lens cells. Co-transfections using Pax6 and c-Maf alone revealed moderate and strong activations of this promoter, respectively. In contrast to synergistic activation of αB-crystallin by Pax6 and c-Maf, Pax6 has a neutral effect on c-Maf-mediated αA-crystallin promoter activation. Chromatin immunoprecipitations established in vivo interactions of Pax6 and c-Maf with the αA-crystallin promoter in lens cells. Collectively, the present data support a molecular model in which tissue-specific expression of αA-crystallin is regulated by recruitment of Pax6 and c-Maf, two proteins regulating multiple processes of lens differentiation, to its promoter. In addition, the data suggest a molecular model of temporal and spatial regulation of αB, αA and γ-crystallin genes in mouse embryonic lens by using variants of the Pax6/ Maf regulatory module.

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Section: Discussionmentioning

confidence: 99%

Tissue-specific Regulation of the Mouse αA-crystallin Gene in Lens via Recruitment of Pax6 and c-Maf to its Promoter

Yang

Cvekl

2005

Journal of Molecular Biology

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“…Insulin secretion is regulated by a variety of transcription factors in pancreatic beta cells (12), such as Pax4 (13), Nkx6.1 (14,15), Maf (16,17), Foxa (18), Pdx1 (19,20), and LIM-homeodomain transcription factor Isl-1 (7), most of which are required for pancreatic development and cell functions (21)(22)(23)(24)(25). A genetic study of a morbidly obese human population suggests that Isl-1 is associated with type 2 diabetes (26).…”

mentioning

confidence: 99%

LIM-homeodomain Transcription Factor Isl-1 Mediates the Effect of Leptin on Insulin Secretion in Mice

Chen

Cui

et al. 2013

Journal of Biological Chemistry

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Background: Leptin and Isl-1 have functions to regulate the insulin secretion, but the interaction between Leptin and Isl-1 remains unknown. Results: Isl-1 mediates the signaling pathway of leptin affecting insulin secretion. Conclusion: Isl-1 and STAT3 are the keynote proteins linking the leptin and insulin signaling networks. Significance: These findings are crucial for understanding the mechanisms of insulin secretion and metabolism.

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“…MAFA is exclusively expressed in b-cells in the pancreas (Kataoka et al 2004, Zhang et al 2005, Nishimura et al 2006 and plays a critical role in establishing b-cell-specific expression of the insulin gene together with the other b-cell-enriched transcription factors, PDX1 and BETA2/NEUROD (Aramata et al 2005, Docherty et al 2005, Kaneto et al 2005. MAFA also regulates a set of b-cell-specific genes, including glucose transporter 2 (glut2) and granuphilin (Zhang et al 2005, Kato et al 2006, Wang et al 2007.…”

Section: Introductionmentioning

confidence: 99%

Proteasome activator PA28γ stimulates degradation of GSK3-phosphorylated insulin transcription activator MAFA

Kanai¹,

Aramata²,

Katakami³

et al. 2011

Journal of Molecular Endocrinology

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MAFA is a member of the MAF family of basic leucine zipper transcription factors and is a critical regulator of insulin gene expression and islet b-cell function. To be degraded by the proteasome, MAFA must be phosphorylated by GSK3 and MAP kinases at multiple serine and threonine residues (Ser49, Thr53, Thr57, Ser61, and Ser65) within its amino-terminal domain. In this study, we report that MAFA degradation is stimulated by PA28g (REGg and PSME3), a member of a family of proteasome activators that bind and activate the 20S proteasome. To date, only a few PA28g-proteasome pathway substrates have been identified, including steroid receptor coactivator 3 (SRC3) and the cell cycle inhibitor p21 (CIP1). PA28g binds to MAFA, induces its proteasomal degradation, and thereby attenuates MAFA-driven transcriptional activation of the insulin promoter. Co-expression of GSK3 enhanced the PA28g-mediated degradation of MAFA, but mutants that contained alanine substitutions at the MAFA phosphorylation sites did not bind PA28g and were resistant to degradation. We also found that a PA28g mutant (N151Y) that did not stimulate p21 degradation enhanced MAFA degradation, and another mutant (K188D) that promoted greater p21 degradation did not enhance MAFA degradation. These results suggest that PA28g stimulates MAFA degradation through a novel molecular mechanism that is distinct from that for the degradation of p21.

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Differentially expressed Maf family transcription factors, c-Maf and MafA, activate glucagon and insulin gene expression in pancreatic islet alpha- and beta-cells

Cited by 78 publications

References 45 publications

Tissue-specific Regulation of the Mouse αA-crystallin Gene in Lens via Recruitment of Pax6 and c-Maf to its Promoter

Tissue-specific Regulation of the Mouse αA-crystallin Gene in Lens via Recruitment of Pax6 and c-Maf to its Promoter

LIM-homeodomain Transcription Factor Isl-1 Mediates the Effect of Leptin on Insulin Secretion in Mice

Proteasome activator PA28γ stimulates degradation of GSK3-phosphorylated insulin transcription activator MAFA

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