TY - JOUR
T1 - Regulation of cytosolic phosphoenolpyruvate carboxykinase gene expression in adipocytes
AU - Beale, Elmus G.
AU - Forest, Claude
AU - Hammer, Robert E.
N1 - Funding Information:
This work was supported by grants to E.G.B. from the NIH (R01-GM39895), Texas Advanced Research Program, and Texas Tech University Health Sciences Center; to C.F. from INSERM, Université René Descartes, the Fondation pour la Recherche Médicale, and the Association pour la Recherche contre le Cancer; and to R.E.H. from the Perot Family Foundation and the Howard Hughes Medical Institute.
PY - 2003/12
Y1 - 2003/12
N2 - Cytosolic phosphoenolpyruvate carboxykinase (EC 4.1.1.32; PEPCK-C) catalyzes the critical regulated step in adipocyte glyceroneogenesis. Numerous studies have shown that hormones and nutrients regulate PEPCK-C at the transcriptional level. We identified two upstream cis-acting DNA elements, gAF1/PCK1 and PCK2, that control adipocyte specific transcription of the PEPCK-C gene (Pck1). Both elements are direct repeat hexanucleotides separated by 1 bp (DR1 elements; variations of the sequence AGGTCAnAGGTCA). PCK2 is located 1 kbp upstream and is the essential element of an adipocyte specific enhancer. It is a peroxisome proliferator activated receptor γ response element (PPRE) and directs the activation of the PEPCK-C gene during adipogenesis. In addition, it is a thiazolidinedione response element in mature adipocytes. In contrast, gAF1/PCK1, centered 445 bp upstream, is a pleiotropic element that mediates tissue specific glucocorticoid action - repression in adipocytes and induction in hepatocytes. It is a negative response element for PPARγ, RXRα, COUP-TFII, and several unidentified proteins in some cell types, and a positive element for COUP-TFI and HNF4 in other cells type. The purpose of this presentation is to review the discovery and characterization of these two elements in adipocytes and describe how our work has contributed to understanding the mechanisms that control adipocyte glyceroneogenesis.
AB - Cytosolic phosphoenolpyruvate carboxykinase (EC 4.1.1.32; PEPCK-C) catalyzes the critical regulated step in adipocyte glyceroneogenesis. Numerous studies have shown that hormones and nutrients regulate PEPCK-C at the transcriptional level. We identified two upstream cis-acting DNA elements, gAF1/PCK1 and PCK2, that control adipocyte specific transcription of the PEPCK-C gene (Pck1). Both elements are direct repeat hexanucleotides separated by 1 bp (DR1 elements; variations of the sequence AGGTCAnAGGTCA). PCK2 is located 1 kbp upstream and is the essential element of an adipocyte specific enhancer. It is a peroxisome proliferator activated receptor γ response element (PPRE) and directs the activation of the PEPCK-C gene during adipogenesis. In addition, it is a thiazolidinedione response element in mature adipocytes. In contrast, gAF1/PCK1, centered 445 bp upstream, is a pleiotropic element that mediates tissue specific glucocorticoid action - repression in adipocytes and induction in hepatocytes. It is a negative response element for PPARγ, RXRα, COUP-TFII, and several unidentified proteins in some cell types, and a positive element for COUP-TFI and HNF4 in other cells type. The purpose of this presentation is to review the discovery and characterization of these two elements in adipocytes and describe how our work has contributed to understanding the mechanisms that control adipocyte glyceroneogenesis.
KW - Diabetes
KW - Glyceroneogenesis
KW - Lipid homeostasis
KW - Obesity
KW - Phosphoenolpyruvate carboxykinase
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U2 - 10.1016/j.biochi.2003.10.012
DO - 10.1016/j.biochi.2003.10.012
M3 - Article
C2 - 14739072
AN - SCOPUS:0346040247
SN - 0300-9084
VL - 85
SP - 1207
EP - 1211
JO - Biochimie
JF - Biochimie
IS - 12
ER -