Lee M Y, Kong H J, Cheong J
Hormone Research Center, Chonnam National University, Kwangju, 500-757, Korea.
Biochem Biophys Res Commun. 2001 Mar;281(5):1241-7. doi: 10.1006/bbrc.2001.4494.
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.
p38β丝裂原活化蛋白激酶活性是3T3-L1成纤维细胞分化为脂肪细胞所必需的。激活转录因子-2（ATF-2）可被p38β激酶有效磷酸化并激活。这些发现促使我们研究ATF-2在脂肪细胞分化中的调节作用。ATF-2蛋白的诱导先于转录因子过氧化物酶体增殖物激活受体（PPAR）γ和CCAAT/增强子结合蛋白（C/EBP）α的表达。与p38β激酶的早期激活一致，在脂肪细胞分化的早期阶段也检测到了ATF-2的磷酸化。ATF-2调节PPARγ的基因转录，p38β激酶和C/EBPβ蛋白的表达可协同增强这种调节作用。在3T3-L1细胞中异位表达ATF-2可诱导内源性PPARγ蛋白水平升高。这些结果表明，ATF-2通过促进包括PPARγ在内的脂肪生成诱导转录因子，在与C/EBPβ共同作为脂肪细胞分化的主要调节因子中发挥作用，并且随着有丝分裂克隆扩增的进行以及细胞开始分化，在分化程序中更早地发挥作用。
