Glucocorticoid regulation of branched-chain α-ketoacid dehydrogenase E2 subunit gene expression

Abstract

Regulation of the mammalian branched-chain α-ketoacid dehydrogenase complex (BCKAD) occurs under a variety of stressful conditions associated with changes in circulating glucocorticoids. Multiple levels of regulation in hepatocytes, including alteration of the levels of the structural subunits available for assembly (E1, α-ketoacid decarboxylase ; E2, dihydrolipoamide acyltransferase ; and E3, dihydrolipoamide dehydrogenase), as well as BCKAD kinase, which serves to phosphorylate the E1α subunit and inactivate complex activity, have been proposed. The direct role of glucocorticoids in regulating the expression of the murine gene encoding the major BCKAD subunit E2, upon which the other BCKAD subunits assemble, was therefore examined. Deletion analysis of the 5« proximal 7.0 kb of the murine E2 promoter sequence, using E2 promoter}luciferase expression minigene plasmids introduced into the hepatic H4IIEC3 cell line, suggested a promoter proximal region responsive to glucocorticoid regulation. Linker-scanning muta-

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Cite this paper

@inproceedings{CosteasGlucocorticoidRO, title={Glucocorticoid regulation of branched-chain α-ketoacid dehydrogenase E2 subunit gene expression}, author={Paul A Costeas and J. Chinsky} }