| Interacting proteins: Q8NHW3 and P52945 |
Pubmed |
SVM Score :1.0342099 |
| MafA interacted with endogenous PDX 1 and BETA 2 in coimmunoprecipitation and in vitro GST pull down assays , suggesting that regulation involved direct binding . 1.0342099^^^ |
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| Interacting proteins: Q8NHW3 and P52945 |
Pubmed |
SVM Score :0.0 |
| Chronic exposure of pancreatic beta cells to elevated glucose reduces insulin gene promoter activity , and this is associated with diminished binding of two beta cell enriched transcription factors , Pdx 1 and MafA . ^^^ In this study using INS 1 beta cells , overexpression of MafA , but not Pdx 1 , was able to restore expression of a human insulin reporter gene ( 327 to +30 bp ) suppressed by elevated glucose . ^^^ The A5 / core binding complex was determined to contain MafA , Pdx 1 , and an A 2 like binding factor . ^^^ Glucose mediated suppression of the Z mini enhancer was not attenuated by overexpression of MafA or Pdx 1 . ^^^ |
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| Interacting proteins: Q8NHW3 and P52945 |
Pubmed |
SVM Score :0.0 |
| In this study , we show that MafA overexpression , together with PDX 1 ( pancreatic and duodenal homeobox factor 1 ) and NeuroD , markedly increases insulin gene expression in the liver . ^^^ Furthermore , in streptozotocin induced diabetic mice , MafA overexpression in the liver , together with PDX 1 and NeuroD , dramatically ameliorated glucose tolerance , while combination of PDX 1 and NeuroD was much less effective . ^^^ |
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| Interacting proteins: Q8NHW3 and P52945 |
Pubmed |
SVM Score :0.0 |
| Additionally , transient transfection of PDX 1 or MafA cDNA into glucotoxic cells increased PDX 1 and MafA protein levels and individually increased insulin promoter activity ( untreated = 34 % , PDX 1 = 70 % , MafA = 78 % ; percentage of activity of early passage cells ) , whereas the combined transfection of MafA and PDX 1 completely restored insulin promoter activity . ^^^ However , adenoviral infection of MafA and PDX 1 significantly increased endogenous insulin mRNA levels by 93 % ( 121 + / 9 versus 233 + / 18 density light units ; n = 5 , p < 0 . 001 ) . ^^^ |
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| Interacting proteins: Q8NHW3 and P52945 |
Pubmed |
SVM Score :0.0 |
| Relative contribution of PDX 1 , MafA and E47 / beta2 to the regulation of the human insulin promoter . ^^^ Of these , the homoeodomain protein PDX 1 ( pancreatic duodenal homeobox factor 1 ) , the basic leucine zipper protein MafA and the basic helix loop helix heterodimer E47 / BETA2 ( beta cell E box transactivator 2 ; referred to here as beta 2 ) bind to important regulatory sites . ^^^ The aim of the present study was to determine the relative contribution of PDX 1 , MafA and E47 / beta2 in regulating the human insulin promoter , and whether these factors could interact synergistically in the context of the human promoter . ^^^ Mutagenesis of the PDX 1 , MafA and E47 / beta2 binding sites reduced promoter activity by 60 , 74 and 94 % respectively , in INS 1 beta cells . ^^^ In the islet glucagonoma cell line alphaTC1 . 6 , overexpression of PDX 1 and MafA separately increased promoter activity approx . 2 . 5 3 fold , and in combination approx . 6 fold , indicating that their overall effect was additive . ^^^ |
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| Interacting proteins: Q8NHW3 and P52945 |
Pubmed |
SVM Score :0.0 |
| Further analysis revealed that insulin 1 , insulin 2 , Pdx 1 , Beta 2 , and Glut 2 transcripts are diminished in MafA deficient mice . ^^^ |
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| Interacting proteins: Q8NHW3 and P52945 |
Pubmed |
SVM Score :0.0 |
| Using MIN 6 beta cells and chromatin immunoprecipitation ( ChIP ) assays , the chronological sequence of binding of MafA , E47 / beta2 and PDX 1 to the insulin promoter in living beta cells were investigated . ^^^ |
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| Interacting proteins: Q8NHW3 and P52945 |
Pubmed |
SVM Score :0.0 |
| Islet beta cell specific transcription of the insulin gene is mediated through the binding of the islet enriched PDX 1 , BETA 2 , and MafA transcription factors to conserved 5 ' flanking region regulatory elements . ^^^ Furthermore , functional interaction analysis in non islet cell lines demonstrated that PDX 1 binding to GG 2 , A 1 , and A 3 contributes to synergistic activation of insulin gene expression with MafA . ^^^ |
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| Interacting proteins: Q8NHW3 and P52945 |
Pubmed |
SVM Score :0.0 |
| Exposure of INS 1 beta cells to elevated glucose leads to reduced insulin gene transcription , and this is associated with diminished binding of pancreatic duodenal homeobox factor 1 ( PDX 1 ) and mammalian homologue of avian MafA / l Maf ( MafA ) . ^^^ Low potency PARP inhibitors restored MafA mRNA and protein levels , but they had no affect on PDX 1 protein levels or binding activity . ^^^ |
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| Interacting proteins: Q8NHW3 and P52945 |
Pubmed |
SVM Score :0.0 |
| Palmitate inhibits insulin gene expression by altering PDX 1 nuclear localization and reducing MafA expression in isolated rat islets of Langerhans . ^^^ This study was designed to assess whether palmitate alters the expression and binding activity of the key regulatory factors pancreas duodenum homeobox 1 ( PDX 1 ) , MafA , and Beta 2 , which respectively bind to the A 3 , C 1 , and E 1 elements in the proximal region of the insulin promoter . ^^^ Combined adenovirus mediated overexpression of PDX 1 and MafA in islets completely prevented the inhibition of insulin gene expression by palmitate . ^^^ These results demonstrate that prolonged exposure of islets to palmitate inhibits insulin gene transcription by impairing nuclear localization of PDX 1 and cellular expression of MafA . . ^^^ |
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| Interacting proteins: Q8NHW3 and P52945 |
Pubmed |
SVM Score :0.0 |
| Synergistic activation of the insulin gene promoter by the beta cell enriched transcription factors MafA , Beta 2 , and Pdx 1 . ^^^ Pdx 1 , MafA , and Beta 2 have been identified as beta cell enriched transcription factors that bind to these elements . ^^^ Among multiple binding sites for Pdx 1 , MafA , and Beta 2 , at least GG 2 , C 1 , and E 1 elements located in the promoter region between 150 and 100 base pairs are necessary for the synergism . ^^^ These results suggest that co expression and functional synergism of these beta cell enriched transactivators , MafA , Pdx 1 , and Beta 2 , are critical for establishing the beta cell specific and efficient expression of the insulin gene . . ^^^ |
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| Interacting proteins: Q8NHW3 and P52945 |
Pubmed |
SVM Score :0.0 |
| The level of mRNAs encoding transcription factors important for insulin gene expression and beta cell function , including MafA , PDX 1 , Nkx6 . 1 , and Pax 6 , was also decreased by cytokine treatment . ^^^ |
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| Interacting proteins: Q8NHW3 and P52945 |
Pubmed |
SVM Score :0.0 |
| The reduction of insulin gene transcription in HIT T 15 beta cells chronically exposed to high glucose concentration is associated with the loss of RIPE3b1 and STF 1 transcription factor expression . ^^^ The results show that the binding and trans activation functions of the RIPE3b1 activator are reduced in parallel with the loss in STF 1 and insulin gene expression . ^^^ Our studies indicate that insulin gene transcription is inhibited by glucose through a mechanism involving reduced expression of both the RIPE3b1 and STF 1 activators in HIT T 15 cells but is independent of the ICE activator . . ^^^ |
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| Interacting proteins: Q8NHW3 and P52945 |
Pubmed |
SVM Score :0.0 |
| We have shown previously that chronic exposure of HIT T 15 cells to supraphysiologic glucose concentrations causes decreased insulin gene transcription and decreased binding activities of two beta cell specific transcription factors , STF 1 and the RIPE3b1 activator , and have suggested that these events may provide a mechanism for glucose toxicity on beta cell function . ^^^ Electromobility shift assays demonstrated that binding of a specific nuclear protein that recognizes the RIPE3b1 binding site of the insulin gene was markedly diminished in late passage cells chronically exposed to 11 . 1 mM glucose , whereas binding activities of STF 1 and ICE activators were unchanged . ^^^ |
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| Interacting proteins: Q8NHW3 and P52945 |
Pubmed |
SVM Score :0.0 |
| Glucose is the major physiologic regulator of insulin gene expression ; it coordinately controls the recruitment of transcription factors [ e . g . , pancreatic / duodenal homeobox 1 ( PDX 1 ) , mammalian homologue of avian MafA / L Maf ( MafA ) , Beta2 / Neuro D ( B 2 ) , the rate of transcription , and the stability of insulin mRNA . ^^^ The mechanisms of glucotoxicity , which involve decreased binding activities of PDX 1 and MafA and increased activity of C / EBPbeta , are mediated by high glucose induced generation of oxidative stress . ^^^ On the other hand , lipotoxicity is mediated by de novo ceramide synthesis and involves inhibition of PDX 1 nuclear translocation and MafA gene expression . ^^^ |
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| Interacting proteins: Q8NHW3 and P52945 |
Pubmed |
SVM Score :0.0 |
| Furthermore , the MafB to MafA transition follows induction of PDX 1 expression ( Pdx 1 ( high ) ) in MafB+ Ins+ cells . ^^^ |
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| Interacting proteins: Q8NHW3 and P52945 |
Pubmed |
SVM Score :0.0 |
| FoxA 2 , Nkx2 . 2 , and PDX 1 regulate islet beta cell specific mafA expression through conserved sequences located between base pairs 8118 and 7750 upstream from the transcription start site . ^^^ Consistent with a role in transcription , small interfering RNA mediated knockdown of PDX 1 led to decreased mafA mRNA production in INS 1 derived beta cell lines ( 832 / 13 and 832 / 3 ) , while MafA expression was undetected in the pancreatic epithelium of Nkx2 . 2 null animals . ^^^ |
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| Interacting proteins: Q8NHW3 and P52945 |
Pubmed |
SVM Score :0.0 |
| In fragment D , cotransfection of oligonucleotide that confers RIPE3b1 activator decreased the glucose stimulated promoter activity , but the other oligonucleotide that confers STF 1 did not . ^^^ |
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| Interacting proteins: Q8NHW3 and P52945 |
Pubmed |
SVM Score :0.0 |
| The islet beta cell enriched RIPE3b1 / Maf transcription factor regulates pdx 1 expression . ^^^ In addition , the chromatin immunoprecipitation assay showed that the Area 2 region of the endogenous pdx 1 gene was precipitated by an antiserum that recognizes the large Maf protein that comprises the RIPE3b1 transcription factor . ^^^ |
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| Interacting proteins: Q8NHW3 and P52945 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: Q8NHW3 and P52945 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q8NHW3 and P52945 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q8NHW3 and P52945 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q8NHW3 and P52945 |
Pubmed |
SVM Score :0.0 |
| NA |
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