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

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.

journal_name

Mol Cell

journal_title

Molecular cell

authors

Herold S,Wanzel M,Beuger V,Frohme C,Beul D,Hillukkala T,Syvaoja J,Saluz HP,Haenel F,Eilers M

doi

10.1016/s1097-2765(02)00633-0

subject

Has Abstract

pub_date

2002-09-01 00:00:00

pages

509-21

issue

3

eissn

1097-2765

issn

1097-4164

pii

S1097-2765(02)00633-0

journal_volume

10

pub_type

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