Negative regulation of the mammalian UV response by Myc through association with Miz-1

被引:257
作者
Herold, S
Wanzel, M
Beuger, V
Frohme, C
Beul, D
Hillukkala, T
Syvaoja, J
Saluz, HP
Haenel, F
Eilers, M [1 ]
机构
[1] Inst Mol Biol & Tumor Res, D-35033 Marburg, Germany
[2] Univ Oulu, Dept Biochem, FIN-90014 Oulu, Finland
[3] Bioctr Oulu, FIN-90014 Oulu, Finland
[4] Hans Knoll Inst Nat Stoff Forsch, Dept Cell & Mol Biol, D-07745 Jena, Germany
基金
芬兰科学院;
关键词
D O I
10.1016/S1097-2765(02)00633-0
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 oncoprotein represses initiator-dependent transcription through the POZ domain transcription factor Miz-1. We now show that transactivation by Miz-1 is negatively regulated by association with topoisomerase II binding protein (TopBP1); UV irradiation downregulates expression of TopBP1 and releases Miz-1. Miz-1 binds to the p21Cip1 core promoter in vivo and is required for upregulation of p21Cip1 upon UV irradiation. Using both c-myc(-/-) cells and a point mutant of Myc that is deficient in Miz-1 dependent repression, we show that Myc negatively regulates transcription of p21Cip1 upon UV irradiation and facilitates recovery from UV-induced cell cycle arrest through binding to Miz-1. Our data implicate Miz-1 in a pathway that regulates cell proliferation in response to UV irradiation.
引用
收藏
页码:509 / 521
页数:13
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