ISSN:
0730-2312
Keywords:
insulin
;
gene transcription
;
GAPDH
;
hormone regulation
;
differentiation-dependent gene expression
;
Life and Medical Sciences
;
Cell & Developmental Biology
Source:
Wiley InterScience Backfile Collection 1832-2000
Topics:
Biology
,
Chemistry and Pharmacology
,
Medicine
Notes:
Insulin induces glyceraldehyde-3-phosphate dehydrogenase (GAPDH) gene transcription in part by regulating one or more proteins that bind a cis-acting element, IRE-A. We have recently cloned a protein, IRE-ABP, that binds the IRE-A element. IRE-ABP is a member of the HMG class of transcriptional regulators and is 67% identical within its HMG box domain to the candidate gene for the testis-determining factor, SRY. IRE-ABP and SRY share binding specificity for the IRE-A motif. This sequence is also highly conserved with a core motif, 5′-Py-ctttg(a/t)-3′, contained in T-cell specific genes that have high affinity for TCF-1α, another member of the HMG class of transcriptional regulators. Thus, diverse members of the HMG family interact with similar nucleotide sequences to regulate expression of genes that initiate and maintain the differentiated phenotype. We have found this core motif in the upstream region of many genes that are positively and negatively regulated by insulin. These observations suggest that IRE-ABP or a related family member may coordinate the expression of these genes. The HMG family of proteins has diverse functions ranging from the regulation of differentiation and mating type in yeast to the regulation of tissue-and species-specific gene expression in mammals. Insulin regulates GAPDH gene transcription in a tissue-specfic manner. We propose that members of the IRE-ABP family play an important role in controlling tissue specificity of the insulin response.
Additional Material:
2 Ill.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1002/jcb.240480204
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