Mayol X, Garriga J, Graña X
Fels Institute for Cancer Research, Temple University School of Medicine, Philadelphia, PA 19140, USA.
Oncogene. 1995 Aug 17;11(4):801-8.
The retinoblastoma-related protein p130 is a putative negative regulator of cell proliferation in mammalian cells. In this study, p130 is shown to exist in multiple phosphorylated forms in human cells. In glioblastoma T98G cells synchronized by serum deprivation, specific phosphorylated forms of p130 are found at different times after serum re-stimulation. Two phosphorylated forms of p130 only found in serum-arrested T98G cells and in early G1 phase associate with the adenovirus oncoprotein E1A in vitro. One of these two forms corresponds to the in vivo E1A-associated p130 in 293 cells, which express endogenous E1A protein. Moreover, p130 undergoes an abrupt shift to a unique phosphorylated form in mid G1 which is the only p130 form found during the remaining phases of the cell cycle. This phosphorylated form possesses an associated histone H1 kinase activity that is most active in late S phase and G2/M. The cell cycle-dependent expression pattern of cyclins in T98G cells is compatible with cyclin D1/CDK complexes driving the shift to this phosphorylated p130 form in mid G1. These results suggest that the putative growth inhibitory function of p130 is regulated by phosphorylation of this protein. They also suggest that differential phosphorylation of p130 during the cell cycle plays distinct roles in the regulation of p130 function.
视网膜母细胞瘤相关蛋白p130被认为是哺乳动物细胞中细胞增殖的负调控因子。在本研究中，p130在人类细胞中以多种磷酸化形式存在。在通过血清剥夺同步化的胶质母细胞瘤T98G细胞中，血清再刺激后不同时间可发现p130的特定磷酸化形式。仅在血清阻滞的T98G细胞和G1早期发现的两种p130磷酸化形式在体外与腺病毒癌蛋白E1A相关联。这两种形式之一与293细胞中体内E1A相关的p130相对应，293细胞表达内源性E1A蛋白。此外，p130在G1中期突然转变为一种独特的磷酸化形式，这是在细胞周期其余阶段发现的唯一p130形式。这种磷酸化形式具有相关的组蛋白H1激酶活性，在S期后期和G2/M期最为活跃。T98G细胞中细胞周期蛋白的细胞周期依赖性表达模式与细胞周期蛋白D1/细胞周期蛋白依赖性激酶复合物在G1中期驱动转变为这种磷酸化p130形式相一致。这些结果表明，p130假定的生长抑制功能受该蛋白磷酸化的调节。它们还表明，细胞周期中p130的差异磷酸化在p130功能调节中发挥着不同作用。
