Transcriptional activities of mutant p53: When mutations are more than a loss

被引:77
作者
Kim, E
Deppert, W
机构
[1] Heinrich Pette Inst, Dept Tumor Biol, D-20251 Hamburg, Germany
[2] Univ Schleswig Holstein, Dept Neurosurg, Neurooncol Grp, Lubeck, Germany
[3] Heinrich Pette Inst, Dept Tumor Virol, D-20251 Hamburg, Germany
关键词
mutant p53; gain-of-function; DNA structure; DNA binding;
D O I
10.1002/jcb.20271
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The dominant oncogenic properties of mutant p53 have been recognized as a phenomenon associated with tumor progression a long time ago, even before it was realized that the major function of wild type p53 is that of a tumor suppressor. Recent advances in this fascinating area in tumor cell biology reveal that the community of mutant p53 proteins is comprised of proteins that are extremely diverse both structurally and functionally, and elicit a multitude of cellular responses that not only are entirely distinct from those mediated by wild type p53, but also vary among different mutant p53 proteins. Aberrant regulation of transcription is one of the mechanisms underlying the ability of some mutant p53 proteins to act as oncogenic factors. Systematic analyses of the transcriptional activities of mutant p53 suggest that not the loss of transcriptional activity as such, but alterations of target DNA selectivity may be the driving force of mutant p53 specific transcription underlying the growth-promoting effects of mutant p53. This article focuses on mechanistic aspects Of mutp53 "gain-of-function" with the emphasis on possible mechanisms underlying transcriptional activation by mutp53. (C) 2004 Wiley-Liss, Inc.
引用
收藏
页码:878 / 886
页数:9
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