Characterization of Functional Domains Necessary for Mutant p53 Gain of Function

作者: Wensheng Yan , Xinbin Chen

DOI: 10.1074/JBC.M109.097253

关键词:

摘要: Tumor cells, including SW480 carcinoma cells that carry a mutant p53, are addicted to the for their survival and resistance growth suppression by chemotherapeutic agents. Here, we investigated whether various classes of p53 mutants share common property functional domains necessary gain function. To test this, generated cell lines in which endogenous R273H/P309S can be inducibly or stably knocked down, whereas small interfering RNA-resistant along with mutated domain expressed. We found both contact-site (R248W R273H) conformation (G245S R249S) able maintain transformed phenotypes conferred p53. also activation 1–2 proline-rich required Interestingly, showed C-terminal basic domain, is wild-type activity, an inhibitory Furthermore, deletion enhances, mutation abolish regulate Gro1 Id2, regulated mediate These results indicate transformation, critical tumor promotion. Thus, explored targeting tumors

参考文章(39)
Mark W. Frazier, Xiaoping He, JinLing Wang, Zhengming Gu, John L. Cleveland, Gerard P. Zambetti, Activation of c-myc Gene Expression by Tumor-Derived p53 Mutants Requires a Discrete C-Terminal Domain Molecular and Cellular Biology. ,vol. 18, pp. 3735- 3743 ,(1998) , 10.1128/MCB.18.7.3735
Arnold J. Levine, Moshe Oren, The first 30 years of p53: growing ever more complex Nature Reviews Cancer. ,vol. 9, pp. 749- 758 ,(2009) , 10.1038/NRC2723
Meredith S Irwin, Keiichi Kondo, Maria Carmen Marin, Lynn S Cheng, William C Hahn, William G Kaelin, Chemosensitivity linked to p73 function Cancer Cell. ,vol. 3, pp. 403- 410 ,(2003) , 10.1016/S1535-6108(03)00078-3
Ran Brosh, Varda Rotter, When mutants gain new powers: news from the mutant p53 field Nature Reviews Cancer. ,vol. 9, pp. 701- 713 ,(2009) , 10.1038/NRC2693
K. K. Walker, A. J. Levine, Identification of a novel p53 functional domain that is necessary for efficient growth suppression Proceedings of the National Academy of Sciences of the United States of America. ,vol. 93, pp. 15335- 15340 ,(1996) , 10.1073/PNAS.93.26.15335
T L Slatter, P Ganesan, C Holzhauer, R Mehta, C Rubio, G Williams, M Wilson, J A Royds, M A Baird, A W Braithwaite, p53-mediated apoptosis prevents the accumulation of progenitor B cells and B-cell tumors Cell Death & Differentiation. ,vol. 17, pp. 540- 550 ,(2010) , 10.1038/CDD.2009.136
Amy Willis, Eun Joo Jung, Therese Wakefield, Xinbin Chen, None, Mutant p53 exerts a dominant negative effect by preventing wild-type p53 from binding to the promoter of its target genes Oncogene. ,vol. 23, pp. 2330- 2338 ,(2004) , 10.1038/SJ.ONC.1207396
N. Baptiste-Okoh, A. M. Barsotti, C. Prives, A role for caspase 2 and PIDD in the process of p53-mediated apoptosis. Proceedings of the National Academy of Sciences of the United States of America. ,vol. 105, pp. 1937- 1942 ,(2008) , 10.1073/PNAS.0711800105