Jiang M S, Lane M D
Department of Biological Chemistry, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Proc Natl Acad Sci U S A. 2000 Nov 7;97(23):12519-23. doi: 10.1073/pnas.220426097.
CCAAT enhancer-binding protein-alpha (C/EBPalpha) functions as a pleiotropic transcriptional activator of adipocyte genes during adipogenesis. Nuclear factor C/EBP undifferentiated protein (CUP), an isoform of activator protein-2alpha (AP-2alpha), binds to repressive elements in the C/EBPalpha gene promoter, silencing the gene until late in the differentiation program. The CUP regulatory element overlaps a Sp (GT-box) element in the promoter to which Sp3 (or Sp1) can bind. Binding by Sp3 or Sp1 and CUP/AP2-alpha is mutually exclusive. Sp3 is a strong transcriptional activator of the C/EBPalpha gene promoter in 3T3-L1 preadipocytes and Schneider cells, this activation being repressed by CUP/AP-2alpha. Sp3 is expressed throughout differentiation, whereas CUP/AP-2alpha, which is expressed only by preadipocytes, is down-regulated during differentiation coincident with transcription of the C/EBPalpha gene. Thus, CUP/AP-2alpha delays access of Sp3 to the Sp regulatory element, preventing premature expression of C/EBPalpha and thereby interference by C/EBPalpha (which is antimitotic) with mitotic clonal expansion, an essential early event in the differentiation program.
CCAAT增强子结合蛋白α（C/EBPα）在脂肪生成过程中作为脂肪细胞基因的多效性转录激活因子发挥作用。核因子C/EBP未分化蛋白（CUP）是激活蛋白-2α（AP-2α）的一种同工型，它与C/EBPα基因启动子中的抑制元件结合，使该基因沉默，直到分化程序后期。CUP调控元件与启动子中的一个Sp（GT盒）元件重叠，Sp3（或Sp1）可以结合到该元件上。Sp3或Sp1与CUP/AP2-α的结合是相互排斥的。Sp3是3T3-L1前脂肪细胞和施奈德细胞中C/EBPα基因启动子的强转录激活因子，这种激活被CUP/AP-2α抑制。Sp3在整个分化过程中都有表达，而仅由前脂肪细胞表达的CUP/AP-2α在分化过程中与C/EBPα基因的转录同时下调。因此，CUP/AP-2α延迟了Sp3与Sp调控元件的结合，防止C/EBPα过早表达，从而防止C/EBPα（具有抗有丝分裂作用）干扰有丝分裂克隆扩增，这是分化程序中一个重要的早期事件。
