Please use this identifier to cite or link to this item:
|Title:||Identification of TopBP1 as a c-Abl-interacting protein and a repressor for c-Abl expression|
|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|
|Appears in Collections:||Staff Publications|
Show full item record
Files in This Item:
There are no files associated with this item.
checked on Aug 18, 2018
WEB OF SCIENCETM
checked on Jul 16, 2018
checked on Mar 11, 2018
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.