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Regulation of pyruvate dehydrogenase kinase 4 (PDK4) by CCAAT/enhancer‐binding protein beta (C/EBPb)
Author(s) -
SHARMA PRAGYA,
ATTIA RAMY R,
SONG SHULAN,
ELAM MARSHALL B,
COOK GEORGE A,
JANSSEN RACHEL C,
FRIEDMAN JACOB E,
PARK EDWARDS A
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.917.5
Subject(s) - pdk4 , pyruvate dehydrogenase complex , ccaat enhancer binding proteins , pyruvate dehydrogenase kinase , pyruvate dehydrogenase lipoamide kinase isozyme 1 , pyruvate dehydrogenase phosphatase , pyruvate kinase , gene knockdown , microbiology and biotechnology , chemistry , biology , gene , biochemistry , glycolysis , transcription factor , enzyme , nuclear protein
Thyroid hormone (T 3 ) regulates various aspects of hepatic metabolism. C/EBPβ modulates the expression of multiple hepatic genes including those involved in hepatic gluconeogenesis. The conversion of pyruvate to acetyl‐CoA in mitochondria is catalyzed by the pyruvate dehydrogenase complex (PDC). Activity of PDC is decreased via phosphorylation by the pyruvate dehydrogenase kinases (PDK). Here we investigated the role of the CCAAT/enhancer‐binding protein β (C/EBPβ) in the T 3 regulation of PDK4 gene expression. Our data indicate that C/EBPβ induces PDK4 gene expression and decreases PDC activity. This transcriptional induction is mediated through C/EBPβ binding sites in the PDK4 promoter. T 3 increased C/EBPβ abundance in primary rat hepatocytes. Knockdown of C/EBPβ with siRNA diminished the T 3 induction of the PDK4. Our data suggest that C/EBPβ is an important accessory factor for the T 3 activation of PDK4 gene.