PI3K/PKB（Akt）信号通路在细胞周期进程中的多重作用。

Multiple roles of the PI3K/PKB (Akt) pathway in cell cycle progression.

作者信息

Liang Jiyong, Slingerland Joyce M

机构信息

Molecular and Cell Biology, Sunnybrook and Women's Health Sciences Centre, University of Toronto, Toronto, Ontario, Canada.

出版信息

Cell Cycle. 2003 Jul-Aug;2(4):339-45.

PMID:12851486

Abstract

As its role in tumor progression emerges, the PI3K/PKB (Akt) pathway presents an appealing cancer therapeutic target. Recent studies have investigated the mechanisms underlying the tumor-promoting effects of this pathway. PKB triggers a network that positively regulates G1/S cell cycle progression through inactivation of GSK3-beta, leading to increased cyclin D1, and inhibition of Forkhead family transcription factors and the tumor suppressor tuberin (TSC2), leading to reduction of p27Kip1. The identification of p21Waf1/Cip1 and p27Kip1 as novel substrates of PKB provided new insights into mechanisms whereby hyperactivation of this lipid signaling pathway may lead to cell cycle deregulation in human cancers. The PI3K pathway may also play a key role in the G2/M transition and its constitutive activation may lead to defects in DNA damage checkpoint control.

摘要

随着PI3K/PKB（Akt）信号通路在肿瘤进展中的作用逐渐显现，它成为了一个颇具吸引力的癌症治疗靶点。近期研究对该信号通路促进肿瘤生长的潜在机制进行了探究。蛋白激酶B（PKB）触发了一个网络，通过使糖原合成酶激酶3β（GSK3-β）失活来正向调控G1/S期细胞周期进程，从而导致细胞周期蛋白D1增加，并抑制叉头家族转录因子和肿瘤抑制因子结节性硬化蛋白2（TSC2），进而使p27Kip1减少。p21Waf1/Cip1和p27Kip1被鉴定为蛋白激酶B的新底物，这为该脂质信号通路过度激活可能导致人类癌症细胞周期失调的机制提供了新见解。PI3K信号通路在G2/M期转换中可能也起着关键作用，其持续性激活可能导致DNA损伤检查点控制出现缺陷。