Regulation of activating transcription factor-2 in early stage of the adipocyte differentiation program.
p38beta mitogen-activated protein kinase activity is required for the differentiation of 3T3-L1 fibroblasts into adipocytes. Activating transcription factor-2 (ATF-2) is efficiently phosphorylated and activated by p38beta kinase. These findings led us to examine a regulatory role of ATF-2 in adipocyte differentiation. The induction of ATF-2 protein precedes the expression of the transcription factors, peroxisome proliferator-activated receptor (PPAR) gamma and CCAAT/enhancer-binding protein (C/EBP) alpha. Consistent with early activation of p38beta kinase, the phosphorylation of ATF-2 was also detected in early stage of adipocyte differentiation. ATF-2 regulated gene transcription of PPARgamma, which was synergistically enhanced by p38beta kinase and C/EBPbeta proteins expression. Ectopic expression of ATF-2 in 3T3-L1 cells induced the endogenous PPARgamma protein levels. These results suggest that ATF-2 plays a role in a primary regulator of adipocyte differentiation with C/EBPbeta through promoting adipogenesis-inducing transcription factors including PPARgamma and becomes associated earlier in the differentiation program as mitotic clonal expansion proceeds and the cells become initially differentiated.
Hormone Research Center, Chonnam National University, Kwangju, 500-757, Korea.
M Y
MY
Lee
H J
HJ
Kong
J
J
Cheong
D051698:Activating Transcription Factor 2; D017667:Adipocytes / Q000166:cytology / Q000378:metabolism*; D000818:Animals; D022782:CCAAT-Enhancer-Binding Protein-beta / Q000378:metabolism; D002454:Cell Differentiation; D002460:Cell Line; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism*; D051379:Mice; D048290:Mitogen-Activated Protein Kinase 11; D020928:Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation; D011401:Promoter Regions, Genetic; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D015533:Transcriptional Activation; D014162:Transfection
D051698:Activating Transcription Factor 2; C497106:Atf2 protein, mouse; D022782:CCAAT-Enhancer-Binding Protein-beta; D017362:Cyclic AMP Response Element-Binding Protein; D018160:Receptors, Cytoplasmic and Nuclear; D014157:Transcription Factors; D048290:Mitogen-Activated Protein Kinase 11; D020928:Mitogen-Activated Protein Kinases