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|Title:||Identification of TopBP1 as a c-Abl-interacting protein and a repressor for c-Abl expression||Authors:||Zeng, L.
|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. https://doi.org/10.1074/jbc.M503016200||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||URI:||http://scholarbank.nus.edu.sg/handle/10635/132790||ISSN:||00219258||DOI:||10.1074/jbc.M503016200|
|Appears in Collections:||Staff Publications|
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