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.
Lee
M Y
MY
Hormone Research Center, Chonnam National University, Kwangju, 500-757, Korea.
Kong
H J
HJ
Cheong
J
J
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