학술논문

Negative Regulation of the Mammalian UV Response by Myc through Association with Miz-1
Document Type
Article
Source
Molecular Cell. Sep2002, Vol. 10 Issue 3, p509. 13p.
Subject
*MYC proteins
*ULTRAVIOLET radiation
*TRANSCRIPTION factors
Language
ISSN
1097-2765
Abstract
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. [Copyright &y& Elsevier]