Myc activation of cyclin E Cdk2 kinase involves induction of cyclin E gene transcription and inhibition of p27(Kip1) binding to newly formed complexes

被引：201

作者：

PerezRoger, I ^{[1
]}

Solomon, DLC ^{[1
]}

Sewing, A ^{[1
]}

Land, H ^{[1
]}

机构：

[1] IMPERIAL CANC RES FUND,LONDON WC2A 3PX,ENGLAND

来源：

ONCOGENE | 1997年 / 14卷 / 20期

关键词：

cell cycle; Cdk2; cyclin E; Myc; p27; Kip1;

D O I：

10.1038/sj.onc.1201197

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Induction of the Myc-oestrogen receptor fusion protein (MycER) by 4-OH-tamoxifen (OHT) leads to the activation of Cyclin E/Cyclin-dependent kinase 2 (CycE/Cdk2) complexes followed by the induction of DNA synthesis. As CycE/Cdk2 activity is essential for G1/S transition, we have investigated the mechanism by which Myc can activiate CycE/Cdk2. Our results suggest that this activation may involve at least two Myc-dependent steps: the induction of cyclin E gene transcription followed by accumulation of cyclin E mRNA in a protein synthesis-independent manner and the inhibition of p27(Kip1) association with CycE/Cdk2 complexes containing newly synthesised CycE. As a consequence phosphorylation of CycE-bound Cdk2 by cyclin activating kinase (CAK) is accelerated. We propose a model in which the active newly synthesised CycE/Cdk2 complexes trigger a positive feed-back mechanism to activate preexisting complexes through phosphorylation-dependent p27(Kip1) release.

引用

页码：2373 / 2381

页数：9

共 59 条

[1] MYC-MAX-MAD - A TRANSCRIPTION FACTOR NETWORK CONTROLLING CELL-CYCLE PROGRESSION, DIFFERENTIATION AND DEATH [J].