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Title: Identification of TopBP1 as a c-Abl-interacting protein and a repressor for c-Abl expression
Authors: Zeng, L.
Hu, Y.
Li, B. 
Issue Date: 12-Aug-2005
Citation: Zeng, L., Hu, Y., Li, B. (2005-08-12). Identification of TopBP1 as a c-Abl-interacting protein and a repressor for c-Abl expression. Journal of Biological Chemistry 280 (32) : 29374-29380. ScholarBank@NUS Repository.
Abstract: Expression of BCR-ABL is the leading cause of chronic myelogenous leukemia. In chronic myelogenous leukemia cells, c-Abl expression is silenced by promoter methylation. In addition, the level of c-Abl needs to be tightly and constantly regulated due to its cytotoxicity and its rapid degradation after activation. Yet the regulation of c-Abl expression remains unclear. In an effort to gain better understanding of c-Abl function, we performed a glutathione S-transferase-Abl pull-down screen and identified TopBP1, a topoisomerase IIβ-binding protein that contains Brca1 C-terminal motifs and has been implicated in DNA damage response. Their physical interaction was verified by in vitro and in vivo assays with TopBP1 found as a substrate of Abl proteins. TopBP1 could repress the expression of c-Abl at both mRNA and protein levels. Reporter assays indicate that TopBP1 directly repressed the promoter activity of c-Abl. Furthermore, TopBP1 repressed expression of c-Abl through a novel mechanism that involved histone deacetylation and DNA methylation. This transcriptional repression was inhibited by c-Abl in a kinase-dependent manner. The dual antagonistic interplay between c-Abl and TopBP1 may also provide a mechanism for fine-tuning of c-Abl levels. © 2005 by The American Society for Biochemistry and Molecular Biology, Inc.
Source Title: Journal of Biological Chemistry
ISSN: 00219258
DOI: 10.1074/jbc.M503016200
Appears in Collections:Staff Publications

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