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PMID: 15075294 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

TopBP1 recruits Brg1/Brm to repress E2F1-induced apoptosis, a novel pRb-independent and E2F1-specific control for cell survival.

Genes & development ·Vol. 18 ·No. 6 ·2004-03-15 ·Pages 673-86

Liu K, Luo Y, Lin FT, Lin WC

Abstract

TopBP1 (DNA topoisomerase IIbeta binding protein I) contains multiple BRCT domains and is involved in replication and the DNA damage checkpoint. Through its BRCT domain, TopBP1 interacts with and represses exclusively E2F1 but not other E2F factors. This regulation of E2F1 transcriptional activity is mediated by a pRb-independent, but Brg1/Brm-dependent mechanism. TopBP1 recruits Brg1/Brm, a central component of the SWI/SNF chromatin-remodeling complex, to E2F1-responsive promoters and represses the activities of E2F1, but not E2F2 or E2F3. This regulation is crucial in the control of E2F1-dependent apoptosis during normal cell growth and DNA damage. Interestingly, TopBP1 is induced by E2F and interacts with E2F1 during G1/S transition. Thus, TopBP1 functions as a critical modulator and serves as a negative feedback regulator of E2F1 by inhibiting E2F1-dependent apoptosis during G1/S transition as well as DNA damage to promote cell survival.

MeSH Terms
Apoptosis/physiology Carrier Proteins/genetics,metabolism Cell Cycle Proteins/metabolism DNA-Binding Proteins Drosophila Proteins E2F Transcription Factors E2F1 Transcription Factor E2F3 Transcription Factor G1 Phase/physiology Gene Expression Regulation Nuclear Proteins/metabolism Promoter Regions, Genetic RNA, Small Interfering S Phase/physiology Trans-Activators/metabolism Transcription Factors/genetics,metabolism
Chemicals
Carrier Proteins Cell Cycle Proteins DNA-Binding Proteins Drosophila Proteins E2F Transcription Factors E2F1 Transcription Factor E2F3 Transcription Factor Nuclear Proteins RNA, Small Interfering TOPBP1 protein, human Trans-Activators Transcription Factors brm protein, Drosophila
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Liu Kang
Division of Hematology and Oncology, Department of Medicine, University of Alabama at Birmingham, AL 35294-3300, USA.
Luo Yuhong
Lin Fang-Tsyr
Lin Weei-Chin
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Article Info
Journal
Genes & development
Abbr.
Genes Dev
ISSN
0890-9369
DOI
10.1101/gad.1180204
Published
2004-03-15
Pages
673-86
Language
English
Region
United States
NLM ID
8711660
PMCID
PMC387242
Subset
IM
Grants
NCI NIH HHS · R01 CA100848 · United States
NCI NIH HHS · R01 CA100857 · United States
NCI NIH HHS · CA100848 · United States
NCI NIH HHS · K12 CA 7693705 · United States
External Links
PubMed source DOI: 10.1101/gad.1180204 PMC Full Text View journal details
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