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Islets 2011MafA, a basic-leucine zipper transcription factor that is important to pancreatic β-cell function, is regulated by several intricate mechanisms. MafA undergoes... (Review)
Review
MafA, a basic-leucine zipper transcription factor that is important to pancreatic β-cell function, is regulated by several intricate mechanisms. MafA undergoes extensive posttranslational modification by phosphorylation, ubiquitination and sumoylation, and these modifications regulate the turnover, DNA binding and transactivation function of the protein. Regulation of MafA expression is equally complex. The initial characterization of the β-cell-specific MafA promoter identified six conserved sequence domains. One of these regions in particular contains consensus motifs and binding sites for several β-cell-enriched transcription factors which ultimately play critical roles in controlling the expression of the gene. Interestingly, in cell culture, acute high glucose stimulation induces the accumulation of MafA, and MafA, in turn, regulates β-cell function. However, under chronic high glucose conditions, which occurs in the context of the diabetic state, β-cell function and, coincidentally, MafA levels decline. Currently, the mechanisms controlling the glucose-dependent accumulation of MafA are not well understood. This commentary highlights a recent report that further defines the regulation of β-cell-specific MafA expression and confirms the longstanding assumption that MafA transcription is upregulated in β-cells acutely cultured in high glucose similar to what may occur in vivo under normoglycemic conditions.
Topics: Animals; Gene Expression Regulation; Glucose; Humans; Insulin-Secreting Cells; Maf Transcription Factors, Large; Mice; Mice, Knockout; Organ Specificity
PubMed: 21278484
DOI: 10.4161/isl.3.1.14032 -
Cellular Signalling Nov 2001We cloned MafG-2, a novel splice variant of MafG, from rat brain by RT-PCR method. MafG-2 differs from the previously published MafG by an insertion of 27 amino acids....
We cloned MafG-2, a novel splice variant of MafG, from rat brain by RT-PCR method. MafG-2 differs from the previously published MafG by an insertion of 27 amino acids. Sequence analysis of the cDNA-encoded MafG-2 showed that MafG-2 contains basic domain and basic leucine zipper (bZip) motif. Transient transfection studies with GFP-MafG-2 chimera protein indicate that MafG-2 is localized in the nuclei of transfected COS-7 cells. To determine whether gene expression of mafG-2 mRNA is induced by an increase in extracellular protons, we analyzed expression of the mRNA in PC12 cells after an increase in extracellular proton concentration. We found that the mafG-2 mRNA expression increased when extracellular pH was decreased gradually from 7.40 to 7.20 and that there was a significant correlation between extracellular pH value and the expression of mafG-2 mRNA. These results suggest that an increase in extracellular proton may induce the expression of mafG-2 mRNA and MafG-2 may be involved in signal transduction of extracellular of H(+).
Topics: Amino Acid Sequence; Animals; Base Sequence; COS Cells; Cloning, Molecular; DNA-Binding Proteins; Extracellular Space; Hydrogen-Ion Concentration; MafG Transcription Factor; Mice; Molecular Sequence Data; Nuclear Proteins; PC12 Cells; Phylogeny; Protons; RNA, Messenger; Rats; Repressor Proteins; Sequence Homology, Amino Acid; Transcription Factors; Transcriptional Activation
PubMed: 11583919
DOI: 10.1016/s0898-6568(01)00213-3 -
Seikagaku. the Journal of Japanese... Apr 2017
Review
Topics: Animals; DNA; Humans; Maf Transcription Factors; Oxidative Stress; Protein Domains; Protein Multimerization
PubMed: 29624997
DOI: No ID Found -
Journal of Immunology (Baltimore, Md. :... Aug 2012Maf proteins are involved in a variety of biological processes, such as oncogenesis, lens development, and differentiation. In immune system, c-Maf transactivates IL-4...
Maf proteins are involved in a variety of biological processes, such as oncogenesis, lens development, and differentiation. In immune system, c-Maf transactivates IL-4 promoter, and ectopic expression of c-Maf skews primary T cell response toward the Th2 pathway. Numerous transcription factors are subjected to posttranslational modification. In this study, to our knowledge, we show for the first time that c-Maf is subjective to tyrosine phosphorylation in Th cells and that the level of its tyrosine phosphorylation positively correlates with IL-4 expression by peripheral Th cells, but is negatively associated with the severity of disease in NOD mice. c-Maf undergoes tyrosine phosphorylation at Tyr(21), Tyr(92), and Tyr(131) residues in Th2 cells. Furthermore, tyrosine phosphorylation at these three residues is critical for the recruitment of c-Maf to IL-4 promoter and IL-4 production in Th cells. Taken together, this study sheds new light on the role of posttranslational modification of c-Maf in IL-4 production and Th cell-mediated autoimmune diseases.
Topics: Animals; Blotting, Western; Diabetes Mellitus, Type 1; Female; Gene Expression Regulation; HEK293 Cells; Humans; Immunoprecipitation; Interleukin-4; Mice; Mice, Inbred NOD; Microscopy, Confocal; Phosphorylation; Protein Processing, Post-Translational; Proto-Oncogene Proteins c-maf; Real-Time Polymerase Chain Reaction; Th2 Cells; Transfection; Tyrosine
PubMed: 22798672
DOI: 10.4049/jimmunol.1200405 -
Stem Cell Research & Therapy Nov 2017Transcription factors regulate gene expression through binding to specific enhancer sequences. Pancreas/duodenum homeobox protein 1 (PDX1), Neurogenin-3 (NEUROG3), and... (Review)
Review
Transcription factors regulate gene expression through binding to specific enhancer sequences. Pancreas/duodenum homeobox protein 1 (PDX1), Neurogenin-3 (NEUROG3), and V-maf musculoaponeurotic fibrosarcoma oncogene homolog A (MAFA) are transcription factors critical for beta cell development and maturation. NEUROG3 is expressed in endocrine progenitor cells and controls islet differentiation and regeneration. PDX1 is essential for the development of pancreatic exocrine and endocrine cells including beta cells. PDX1 also binds to the regulatory elements and increases insulin gene transcription. Likewise, MAFA binds to the enhancer/promoter region of the insulin gene and drives insulin expression in response to glucose. In addition to those natural roles in beta cell development and maturation, ectopic expression of PDX1, NEUROG3, and/or MAFA has been successfully used to reprogram various cell types into insulin-producing cells in vitro and in vivo, such as pancreatic exocrine cells, hepatocytes, and pluripotent stem cells. Here, we review biological properties of PDX1, NEUROG3, and MAFA, and their applications and limitations for beta cell regenerative approaches. The primary source literature for this review was acquired using a PubMed search for articles published between 1990 and 2017. Search terms include diabetes, insulin, trans-differentiation, stem cells, and regenerative medicine.
Topics: Acinar Cells; Animals; Basic Helix-Loop-Helix Transcription Factors; Cell Differentiation; Cell Transdifferentiation; Cell- and Tissue-Based Therapy; Cellular Reprogramming; Diabetes Mellitus; Gene Expression Regulation; Hepatocytes; Homeodomain Proteins; Humans; Insulin; Insulin-Secreting Cells; Maf Transcription Factors, Large; Mice; Nerve Tissue Proteins; Pluripotent Stem Cells; Signal Transduction; Trans-Activators
PubMed: 29096722
DOI: 10.1186/s13287-017-0694-z -
International Journal of Molecular... Nov 2015Protein transduction using cell-penetrating peptides (CPPs) is useful for the delivery of large protein molecules, including some transcription factors. This method is... (Review)
Review
Protein transduction using cell-penetrating peptides (CPPs) is useful for the delivery of large protein molecules, including some transcription factors. This method is safer than gene transfection methods with a viral vector because there is no risk of genomic integration of the exogenous DNA. Recently, this method was reported as a means for the induction of induced pluripotent stem (iPS) cells, directing the differentiation into specific cell types and supporting gene editing/correction. Furthermore, we developed a direct differentiation method to obtain a pancreatic lineage from mouse and human pluripotent stem cells via the protein transduction of three transcription factors, Pdx1, NeuroD, and MafA. Here, we discuss the possibility of using CPPs as a means of directing the differentiation of iPS cells and other stem cell technologies.
Topics: Animals; Basic Helix-Loop-Helix Transcription Factors; Cell Differentiation; Cell-Penetrating Peptides; Cellular Reprogramming; Cinnamates; Gene Expression; Glucagon-Like Peptide 1; Homeodomain Proteins; Humans; Induced Pluripotent Stem Cells; Insulin-Secreting Cells; Intercellular Signaling Peptides and Proteins; Maf Transcription Factors, Large; Mice; Nerve Tissue Proteins; Niacinamide; Trans-Activators; Tretinoin; Veratrum Alkaloids
PubMed: 26561805
DOI: 10.3390/ijms161125986 -
Hormone and Metabolic Research =... Sep 2007Post-translational attachment of small ubiquitin-like modifier (SUMO), defined as SUMOylation, can affect the localization, interactions, stability and/or activity of... (Review)
Review
Post-translational attachment of small ubiquitin-like modifier (SUMO), defined as SUMOylation, can affect the localization, interactions, stability and/or activity of substrate proteins, and thus can participate in a large variety of cellular processes. Most SUMO substrates are involved in transcriptional regulation. Hence, SUMOylation can either activate or, more commonly, repress gene transcription. The modulation of gene expression by SUMO through diverse mechanisms and specifically the recent findings concerning SUMOylation in pancreatic beta-cells are reviewed.
Topics: DNA-Binding Proteins; Diabetes Mellitus, Type 1; Gene Expression Regulation; Genetic Predisposition to Disease; Homeodomain Proteins; Humans; Insulin; Insulin-Secreting Cells; Maf Transcription Factors, Large; Models, Biological; Protein Binding; Protein Conformation; Protein Processing, Post-Translational; Protein Transport; Receptor-Like Protein Tyrosine Phosphatases, Class 8; SUMO-1 Protein; Saccharomyces cerevisiae; Signal Transduction; Trans-Activators
PubMed: 17846973
DOI: 10.1055/s-2007-985372 -
Current Diabetes Reviews 2015Pancreatic β-cells secrete insulin when blood glucose levels become high. However, when β-cells are chronically exposed to hyperglycemia, their function gradually... (Review)
Review
Pancreatic β-cells secrete insulin when blood glucose levels become high. However, when β-cells are chronically exposed to hyperglycemia, their function gradually deteriorates. Although such phenomena are called as β-cell glucose toxicity, its molecular mechanism remained unclear. This manuscript describes the possible mechanism for such β-cell dysfunction. In the diabetic state, nuclear expression levels of pancreatic transcription factors PDX-1 and MafA are decreased. In addition, incretin receptor expression in β- cells is decreased, which is likely involved in the impairment of incretin effects in diabetes. Taken together, it is likely that down-regulation of pancreatic transcription factors and/or incretin receptors are involved in β-cell dysfunction observed in type 2 diabetes.
Topics: Diabetes Mellitus, Type 2; Down-Regulation; Glucose; Homeodomain Proteins; Humans; Hyperglycemia; Insulin-Secreting Cells; Maf Transcription Factors, Large; Oxidative Stress; Trans-Activators
PubMed: 25515340
DOI: 10.2174/1573399811666141216160217 -
Pest Management Science Jul 2014Increased insecticide detoxification mediated by cytochrome P450s is a common mechanism of insecticide resistance. Although Cyp6a2 has been observed to be overexpressed...
BACKGROUND
Increased insecticide detoxification mediated by cytochrome P450s is a common mechanism of insecticide resistance. Although Cyp6a2 has been observed to be overexpressed in many 4,4'-dichlorodiphenyltrichloroethane (DDT)-resistant strains of Drosophila melanogaster, how Cyp6a2 is regulated and whether its overproduction confers DDT resistance remain elusive.
RESULTS
Molecular analysis identified five Cyp6a2 alleles (Cyp6a2(Canton) (-S-1) , Cyp6a2(Canton) (-S-2) , Cyp6a2(91-C) , Cyp6a2(91-R) and Cyp6a2(Wisconsin) (-) (WD) ) from four D. melanogaster strains, notably differing in the presence or absence of an intact Nrf2/Maf (a transcription factor) binding site in the 5'-promoter core region, a 'G1410' frameshift deletion mutation in the heme-binding region and a long terminal repeat (LTR) of transposable element 17.6 in the 3'-untranslated region (UTR). Linkage analysis confirmed that DDT resistance was genetically linked to a Nrf2/Maf-binding-site-containing, LTR-lacking functional allele of Cyp6a2 (Cyp6a2(91-R) ). The qRT-PCR results showed that overexpression of functional Cyp6a2 was consistently associated with DDT resistance. Luciferase reporter gene assays revealed that an intact Nrf2/Maf binding site in the 5'-promoter core region enhanced the constitutive transcription of Cyp6a2.
CONCLUSION
The results suggest that the Nrf2/Maf binding-site-containing functional Cyp6a2 allele is associated with DDT resistance in the D. melanogaster strains under study.
Topics: Animals; Base Sequence; Cytochrome P-450 Enzyme System; Cytochrome P450 Family 6; DDT; Drosophila Proteins; Drosophila melanogaster; Female; Insecticide Resistance; Insecticides; Maf Transcription Factors; Molecular Sequence Data; Real-Time Polymerase Chain Reaction; Sequence Alignment
PubMed: 24038867
DOI: 10.1002/ps.3645 -
Biochemical and Biophysical Research... Jan 2001The Maf protein family consists of eight transcription factors containing a basic-leucine zipper (bZIP) domain. We have previously reported that the mRNA to one of these...
The Maf protein family consists of eight transcription factors containing a basic-leucine zipper (bZIP) domain. We have previously reported that the mRNA to one of these members, mafG/adapt66, is induced by oxidative stress in hamster HA-1 cells. It has subsequently been reported that mafG is induced bystress that activates the expression of genes under the control of the antioxidant/electrophile response element (ARE/EpRE), and that small Maf proteins are present in ARE/EpRE-protein complexes. Here we extend these studies to assess the effects of various types of stress on maf mRNA induction in human cells. The oxidative stressor cadmium, and the heavy metals cadmium, zinc, and arsenite induced mafG RNA levels within two hours, and maximally at five hours for cadmium and zinc. This induction was observed for multiple transcripts including two not normally associated with mafG, suggesting that these stress agents induced the expression of other related maf family RNAs. Modest induction of mafG mRNA was also observed with heat shock but not calcium elevation. These results suggest that mafG is a human stress-response gene induced by multiple stress, and that several maf (proto-)oncogene members play an important role in cellular stress response.
Topics: Animals; Arsenites; Cadmium Chloride; Calcimycin; Chlorides; Cricetinae; DNA-Binding Proteins; Gene Expression Regulation; HSP70 Heat-Shock Proteins; HeLa Cells; Hot Temperature; Humans; Kinetics; MafG Transcription Factor; Metals, Heavy; Oxidative Stress; Proto-Oncogene Mas; RNA, Messenger; Repressor Proteins; Sodium Compounds; Transcription, Genetic; Zinc Compounds
PubMed: 11162468
DOI: 10.1006/bbrc.2000.4064