Holt E H, Lane M D
Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
Biochem Biophys Res Commun. 2001 Nov 9;288(4):752-6. doi: 10.1006/bbrc.2001.5846.
Activation of transcription of the C/EBPalpha (CCAAT/enhancer binding protein alpha) gene is a critical event in the differentiation of 3T3-L1 preadipocytes into adipocytes. The kinetics of this process parallels a decline of AP-2alpha protein (also referred to as CUP, C/EBP undifferentiated protein) and decreased binding of CUP/AP-2alpha to the C/EBPalpha promoter. Mutation of the CUP/AP-2 binding sites in the C/EBPalpha promoter results in increased C/EBPalpha expression. Based on these findings, it appears that decline in AP-2alpha expression is an important early event in the adipocyte differentiation program. In the studies presented here, we identify three mRNAs that encode the repressive CUP/AP-2alpha isoforms expressed in undifferentiated 3T3-L1 preadipocytes. We demonstrate that the kinetics of the decline of these isoforms' expression over the course of differentiation parallels both the decrease in CUP/AP-2alpha DNA binding activity and the increase in C/EBPalpha protein observed in previous studies.
C/EBPα（CCAAT/增强子结合蛋白α）基因转录的激活是3T3-L1前脂肪细胞分化为脂肪细胞过程中的关键事件。这一过程的动力学与AP-2α蛋白（也称为CUP，C/EBP未分化蛋白）的减少以及CUP/AP-2α与C/EBPα启动子结合的减少相平行。C/EBPα启动子中CUP/AP-2结合位点的突变导致C/EBPα表达增加。基于这些发现，AP-2α表达的下降似乎是脂肪细胞分化程序中的一个重要早期事件。在本文所述的研究中，我们鉴定出三种mRNA，它们编码在未分化的3T3-L1前脂肪细胞中表达的抑制性CUP/AP-2α亚型。我们证明，在分化过程中这些亚型表达下降的动力学与之前研究中观察到的CUP/AP-2α DNA结合活性的降低以及C/EBPα蛋白的增加相平行。
