Viadiu Hector
Department of Chemistry and Biochemistry, University of California San Diego, 9500 Gilman Dr. MC 0378, La Jolla, CA 92093, USA.
Curr Top Med Chem. 2008;8(15):1327-34. doi: 10.2174/156802608786141160.
p53 is a transcription factor central to cellular DNA metabolism that controls cellular responses to DNA damage. p53 activity, finely regulated, integrates the information from several pathways to preserve the cell's genetic information. Great attention has been given to the structural determination of p53 domains and its cancerous mutants because 50% of cancer cases present mutations in p53 that hinder its activity resulting in uncontrolled cell reproduction. We enumerate the multiple studies carried to elucidate the structure of p53 domains and we highlight their main findings. The ultimate goal of the reviewed structural efforts is to understand p53 function at atomic level with the aim to overcome cancer by reversing p53 mutant activity to its normal function.
p53是细胞DNA代谢的核心转录因子,可控制细胞对DNA损伤的反应。p53的活性受到精细调节,它整合来自多个途径的信息以保存细胞的遗传信息。人们对p53结构域及其癌性突变体的结构测定给予了极大关注,因为50%的癌症病例中p53存在突变,这些突变会阻碍其活性,导致细胞不受控制地繁殖。我们列举了为阐明p53结构域结构所进行的多项研究,并突出了它们的主要发现。这些经综述的结构研究的最终目标是在原子水平上理解p53的功能,以期通过将p53突变体的活性恢复到正常功能来攻克癌症。