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

S Herold, M Wanzel, V Beuger, C Frohme, D Beul… - Molecular cell, 2002 - cell.com
S Herold, M Wanzel, V Beuger, C Frohme, D Beul, T Hillukkala, J Syvaoja, HP Saluz…
Molecular cell, 2002cell.com
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 …
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.
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