Zhang, H. and Xu, Y. and Filipovic, A. and Lit, Lei Cheng and Koo, C.Y. and Stebbing, J. and Giamas, G. (2013) SILAC-based phosphoproteomics reveals an inhibitory role of KSR1 in p53 transcriptional activity via modulation of DBC1. British Journal of Cancer, 109 (10). pp. 2675-2684. ISSN 0007-0920, DOI https://doi.org/10.1038/bjc.2013.628.
Full text not available from this repository.Abstract
Background:We have previously identified kinase suppressor of ras-1 (KSR1) as a potential regulatory gene in breast cancer. KSR1, originally described as a novel protein kinase, has a role in activation of mitogen-activated protein kinases. Emerging evidence has shown that KSR1 may have dual functions as an active kinase as well as a scaffold facilitating multiprotein complex assembly. Although efforts have been made to study the role of KSR1 in certain tumour types, its involvement in breast cancer remains unknown.Methods:A quantitative mass spectrometry analysis using stable isotope labelling of amino acids in cell culture (SILAC) was implemented to identify KSR1-regulated phosphoproteins in breast cancer. In vitro luciferase assays, co-immunoprecipitation as well as western blotting experiments were performed to further study the function of KSR1 in breast cancer.Results:Of significance, proteomic analysis reveals that KSR1 overexpression decreases deleted in breast cancer-1 (DBC1) phosphorylation. Furthermore, we show that KSR1 decreases the transcriptional activity of p53 by reducing the phosphorylation of DBC1, which leads to a reduced interaction of DBC1 with sirtuin-1 (SIRT1); this in turn enables SIRT1 to deacetylate p53.Conclusion:Our findings integrate KSR1 into a network involving DBC1 and SIRT1, which results in the regulation of p53 acetylation and its transcriptional activity. © 2013 Cancer Research UK. All rights reserved.
| Item Type: | Article |
|---|---|
| Funders: | UNSPECIFIED |
| Uncontrolled Keywords: | Amino Acids; Breast Neoplasms; Cell Culture Techniques; Down-Regulation; Female; Gene Expression Regulation, Neoplastic; HCT116 Cells; Humans; Isotope Labeling; Phosphoproteins; Protein Kinases; Proteomics; Sirtuin 1; Transcriptional Activation; Tumor Cells, Cultured; Tumor Suppressor Protein p53; Tumor Suppressor Proteins |
| Subjects: | R Medicine |
| Divisions: | Faculty of Medicine |
| Depositing User: | Ms. Juhaida Abd Rahim |
| Date Deposited: | 20 Nov 2019 03:09 |
| Last Modified: | 20 Nov 2019 03:09 |
| URI: | http://eprints.um.edu.my/id/eprint/23075 |
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