Miz1 and HectH9 regulate the stability of the checkpoint protein, TopBP1

被引：71

作者：

Herold, Steffi ^{[1
]}

Hock, Andreas ^{[1
]}

Herkert, Barbara ^{[1
]}

Berns, Katrien ^{[2
]}

Mullenders, Jasper ^{[2
]}

Beijersbergen, Roderick ^{[2
]}

Bernards, Rene ^{[2
]}

Eilers, Martin ^{[1
]}

机构：

[1] Univ Marburg, Inst Mol Biol & Tumor Res, D-35033 Marburg, Germany

[2] Netherlands Canc Inst, Div Mol Carcinogenesis, Amsterdam, Netherlands

来源：

EMBO JOURNAL | 2008年 / 27卷 / 21期

关键词：

Atr; Miz1; Myc; TopBP1;

D O I：

10.1038/emboj.2008.200

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：

The Myc-associated zinc-finger protein, Miz1, activates transcription of the p21cip1 gene in response to UV irradiation. Miz1 associates with topoisomerase II binding protein1 (TopBP1), an essential activator of the Atr kinase. We show here that Miz1 is required for the recruitment of a fraction of TopBP1 to chromatin, for the protection of TopBP1 from proteasomal degradation and for Atr-dependent signal transduction. TopBP1 that is not bound to chromatin is degraded by the HectH9 ( Mule, ARF-BP1 and HUWE1) ubiquitin ligase. Myc antagonizes the binding of TopBP1 to Miz1; as a result, expression of Myc leads to dissociation of TopBP1 from chromatin, reduces the amount of total TopBP1 and attenuates Atr-dependent signal transduction. Our data show that Miz1 and Myc affect the activity of the Atr checkpoint through their effect on TopBP1 chromatin association and stability.

引用

页码：2851 / 2861

页数：11