Hannon G J, Beach D
Howard Hughes Medical Institute, Cold Spring Harbor Laboratory, New York 11724.
Nature. 1994 Sep 15;371(6494):257-61. doi: 10.1038/371257a0.
Transforming growth factor-beta (TGF-beta) inhibits cell proliferation by inducing a G1-phase cell cycle arrest. Normal progression through G1 is promoted by the activity of the cyclin-dependent protein kinases CDK4 and CDK6 (ref. 2), which are inhibited by the protein p16INK4. We have isolated a new member of the p16INK4 family, p15INK4B. p15 expression is induced approximately 30-fold in human keratinocytes by treatment with TGF-beta, suggesting that p15 may act as an effector of TGF-beta-mediated cell cycle arrest. The gene encoding p15 is located on chromosome 9 adjacent to the p16 gene at a frequent site of chromosomal abnormality in human tumours (9p21).
转化生长因子-β（TGF-β）通过诱导G1期细胞周期停滞来抑制细胞增殖。细胞周期蛋白依赖性蛋白激酶CDK4和CDK6的活性促进了细胞正常通过G1期（参考文献2），而这两种激酶受到蛋白p16INK4的抑制。我们分离出了p16INK4家族的一个新成员——p15INK4B。用TGF-β处理后，人角质形成细胞中p15的表达可被诱导增加约30倍，这表明p15可能作为TGF-β介导的细胞周期停滞的效应因子发挥作用。编码p15的基因位于9号染色体上，与p16基因相邻，该区域是人类肿瘤中染色体异常的常见位点（9p21）。
