Lyle R E, Richon V M, McGehee R E
Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, Arkansas, 72205, USA.
Biochem Biophys Res Commun. 1998 Jun 18;247(2):373-8. doi: 10.1006/bbrc.1998.8773.
The inhibitory effects of TNFalpha on adipocyte differentiation are well described, however, the mechanisms are poorly understood. Early during hormonally-induced 3T3-L1 preadipocyte differentiation there is a requisite mitotic clonal expansion phase that is associated with significant regulation in p130 and p107 protein levels, two members of the retinoblastoma protein family that regulate cell cycle events through interactions with the E2F transcription factors. This regulation occurs within the first 24 hours of differentiation (Day 1) and is characterized by a transient increase in p107 protein and mRNA levels as well as a transient decrease in p130 protein levels. Here we describe that TNFalpha disrupts the normal pattern of expression of both p130 and p107 proteins, leading to a complete block in mitotic clonal expansion. Interestingly, TNFalpha-treated cells enter S-phase as determined by 5-bromo-2'-deoxyuridine uptake experiments, but rather than completing cell cycle, they are stimulated to undergo apoptosis.
肿瘤坏死因子α（TNFα）对脂肪细胞分化的抑制作用已有充分描述，然而其机制却知之甚少。在激素诱导的3T3-L1前脂肪细胞分化早期，存在一个必要的有丝分裂克隆扩增阶段，这与视网膜母细胞瘤蛋白家族的两个成员p130和p107蛋白水平的显著调节有关，这两个成员通过与E2F转录因子相互作用来调节细胞周期事件。这种调节发生在分化的最初24小时（第1天）内，其特征是p107蛋白和mRNA水平短暂升高，以及p130蛋白水平短暂降低。在此我们描述，TNFα破坏了p130和p107蛋白的正常表达模式，导致有丝分裂克隆扩增完全受阻。有趣的是，通过5-溴-2'-脱氧尿苷摄取实验确定，经TNFα处理的细胞进入S期，但它们不是完成细胞周期，而是被刺激发生凋亡。
