P205, A potential, tumor suppressor, inhibits cell proliferation via multiple pathways of cell cycle regulation
P205, A potential, tumor suppressor, inhibits cell proliferation via multiple pathways of cell cycle regulation
复制标题
DOI：
10.1016/j.febslet.2006.01.032
复制
发表时间：
2006-02-01
期刊：
影响因子：
3.5
通讯作者：
Keller, JR
中科院分区：
文献类型：
--
作者：
Asefa, B;Dermott, JM;Keller, JR
p205是调节细胞增殖的蛋白质诱导型蛋白质家族的成员。 P205的过表达抑制了细胞的生长，尽管其作用机理目前尚不清楚。因此，我们评估了p205对细胞周期调节的p53和Rb依赖性途径的影响。 p205表达会导致p21水平升高，并以p53依赖性方式在体外激活p21启动子。另外，p205诱导RB的表达增加，并直接与RB和p53结合。有趣的是，P205还通过延迟增殖细胞中G21M进展，诱导与P53和RB无关的生长抑制作用，并且是CDK2激酶活性的底物。最后，我们通过酵母双杂交筛网（包括配对的同源域HOXB2）确定了P205的其他结合伴侣。综上所述，我们的结果表明，P205通过与调节细胞周期的多个转录因子的相互作用诱导生长停滞，包括但不完全取决于RB和P53介导的生长抑制途径。 （c）2006年欧洲生化社会联合会。由Elsevier B.V.保留所有权利。
p205 is a member of the interferon-inducible p200 family of proteins that regulate cell proliferation. Over-expression of p205 inhibits cell growth, although its mechanism of action is currently unknown. Therefore, we evaluated the effect of p205 on the p53 and Rb-dependent pathways of cell cycle regulation. p205 expression results in elevated levels of p21, and activates the p21 promoter in vitro in a p53-dependent manner. In addition, p205 induces increased expression of Rb, and binds directly to Rb and p53. Interestingly, p205 also induces growth inhibition independent of p53 and Rb by delaying G21M progression in proliferating cells, and is a substrate for Cdk2 kinase activity. Finally, we have identified other binding partners of p205 by a yeast two-hybrid screen, including the paired homeodomain protein HoxB2. Taken together, our results indicate that p205 induces growth arrest by interaction with multiple transcription factors that regulate the cell cycle, including but not entirely dependent on the Rb- and p53-mediated pathways of growth inhibition. (c) 2006 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.