Identification of a 30-Base Pair Regulatory Element and Novel DNA Binding Protein That Regulates the Human GLUT4 Promoter in Transgenic Mice

Oshel, Katherine M.; Knight, John; Cao, Kim T.; Thai, Martin V.; Olson, Ann Louise

doi:10.1074/jbc.m001452200

Cited by 87 publications

(110 citation statements)

References 38 publications

Supporting

Mentioning

105

Contrasting

Order By: Relevance

“…The GLUT4 gene is subjected to a complex system of tissuespecific and metabolic regulation. Two regulatory domains of the 5′-flanking DNA region are required to direct a complete programme of GLUT4 gene regulation [7][8][9][10]. The region referred to as domain II or myocyte enhancer factor 2 (MEF2) domain binds the isoforms of the MEF2 family of transcription factors (MEF2A, MEF2B, MEF2C and MEF2D) [11][12][13].…”

Section: Introductionmentioning

confidence: 99%

The glucose-lowering agent sodium tungstate increases the levels and translocation of GLUT4 in L6 myotubes through a mechanism associated with ERK1/2 and MEF2D

et al. 2008

View full text Add to dashboard Cite

Aims/hypothesis The aim of this study was to investigate the action of the glucose-lowering compound sodium tungstate on glucose transport in muscle myotubes and to unravel the molecular events underlying the effects observed. Methods We studied the effects of tungstate on 2-deoxy-Dglucose uptake, levels and translocation of the glucose transporters GLUT4 and GLUT1, and Glut4 (also known as Slc2a4) promoter activity. We also measured the modifications of individual components of the signalling pathways involved in the effects observed. Results Tungstate increased 2-deoxy-D-glucose uptake in differentiated L6 myotubes through an increase in the total amount and translocation of GLUT4 transporter. The effects on glucose uptake were additive to those of insulin. Tungstate activated transcription of the Glut4 promoter, as shown by an increase in Glut4 mRNA, and by a promoter reporter assay. The assay of deletions of the Glut4 promoter indicated that the effect of tungstate is mediated by the myocyte enhancer factor 2 (MEF2)-binding domain. Accordingly, MEF2 levels and DNA binding activities were increased in response to the treatment. Tungstate-induced glucose uptake and GLUT4 transcriptional activation were dependent on the activation of extracellular signal-regulated kinases 1 and 2 (ERK1/2), while no changes were observed in the phosphorylation state of the β subunit of the insulin receptor, in the phosphatidylinositol 3-kinase pathway or in the activation of 5′AMP-activated protein kinase. Conclusions/interpretation Tungstate activates glucose uptake in myotubes through a novel ERK1/2-dependent mechanism. This effect is exerted by an increase in the content and translocation of the GLUT4 transporter. This is the first report of a glucose-lowering compound activating Glut4 transcription through an ERK1/2-dependent increase in MEF2 levels.

show abstract

Section: Introductionmentioning

confidence: 99%

The glucose-lowering agent sodium tungstate increases the levels and translocation of GLUT4 in L6 myotubes through a mechanism associated with ERK1/2 and MEF2D

et al. 2008

View full text Add to dashboard Cite

show abstract

“…The first, a 513-amino acid protein called papillomavirus regulatory factor (Prf-1) and papillomavirus binding factor (PBF) was identified in a yeast one-hybrid assay for cellular proteins binding to the E2 binding site, P2, of human papillomavirus type 8 (29). The second factor, GLUT4-enhancer factor (G4EF), is highly similar to Prf-1/PBF and was identified as a 387-amino acid DNA-binding protein that recognizes the enhancer for the human GLUT4 transporter gene (30). On the basis of a CX 4 C-X 12 H-X 4 H sequence in the middle portion of each protein, both Prf-1/PBF and G4EF are proposed to contain a TFIIIA-like zinc finger DNA-binding domain.…”

Section: Figmentioning

confidence: 99%

A New β-Catenin-dependent Activation Domain in T Cell Factor

Atcha

Munguia

et al. 2003

Journal of Biological Chemistry

View full text Add to dashboard Cite

Transcription of the lymphoid enhancer factor-1 (LEF1) gene is aberrantly activated in sporadic colon cancer, whereas this gene is not expressed in the normal adult colon. We have shown previously that promoter 1 of the LEF1 gene is activated by T cell factor (TCF)-␤-catenin complexes in transient transfection assays, suggesting that LEF1 is a target of the Wnt pathway in colon cancer. To further explore the link between LEF1 expression and the Wnt pathway, we studied two response elements in the promoter. Surprisingly we found that the LEF1 promoter is selectively activated by specific isoforms of the LEF/TCF transcription factor family that contain an alternative C-terminal "E" tail. These isoforms, TCF-1E and TCF-4E, activate the promoter in a ␤-catenin-dependent manner. We show that a complete E-tail domain is necessary for full activity and delimits residues within two highly conserved peptide motifs within the tail that are required (KKCRARFG; WCXX-CRRKKKC). These peptide motifs are not only conserved among the TCF family members but are also found in two newly identified DNA-binding proteins named papillomavirus binding factor and GLUT4 enhancer factor. This study thus identifies a new and unique set of motifs used by the Wnt pathway for target gene regulation.

show abstract

“…GEF is a transcriptional activator that binds to domain I of the GLUT4 gene promoter (41,55). Coimmunoprecipitation and transient transfection assays demonstrated that GEF and MEF2A exert synergistic activation of the GLUT4 gene promoter by interacting with each other.…”

Section: Muscle-specific Glut4 Enhancer Factor (Gef)mentioning

confidence: 99%

Regulation of glucose transporter type 4 isoform gene expression in muscle and adipocytes

Kwon

Kim

et al. 2007

IUBMB Life

View full text Add to dashboard Cite

SummaryThe gene expression of glucose transporter type 4 isoform (GLUT4) is known to be controlled by metabolic, nutritional, or hormonal status. Understanding the molecular mechanisms governing GLUT4 gene expression is critical, because glucose disposal in the body depends on the activities of GLUT4 in the muscle and adipocytes. The GLUT4 activities are regulated by a variety of mechanisms. One of them is transcriptional regulation. GLUT4 gene expression is regulated by a variety of transcriptional factors in muscle and adipose tissue. These data are accumulating regarding the transcriptional factors regulating GLUT4 gene expression. These include MyoD, MEF2A, GEF, TNF-a, TR-1a, KLF15, SREBP-1c, C/EBP-a, O/E-1, free fatty acids, PAPRg, LXRa, NF-1, etc. These factors are involved in the positive or negative regulation of GLUT4 gene expression. In addition, there is a complex interplay between these factors in transactivating GLUT4 promoter activity. Understanding the mechanisms controlling GLUT4 gene transcription in these tissues will greatly promote the potential therapeutic drug development for obesity and T2DM.

show abstract

Identification of a 30-Base Pair Regulatory Element and Novel DNA Binding Protein That Regulates the Human GLUT4 Promoter in Transgenic Mice

Cited by 87 publications

References 38 publications

The glucose-lowering agent sodium tungstate increases the levels and translocation of GLUT4 in L6 myotubes through a mechanism associated with ERK1/2 and MEF2D

The glucose-lowering agent sodium tungstate increases the levels and translocation of GLUT4 in L6 myotubes through a mechanism associated with ERK1/2 and MEF2D

A New β-Catenin-dependent Activation Domain in T Cell Factor

Regulation of glucose transporter type 4 isoform gene expression in muscle and adipocytes

Contact Info

Product

Resources

About