Vaseva Angelina V, Moll Ute M
Department of Pathology, Stony Brook University, Stony Brook, NY 11794, USA.
Biochim Biophys Acta. 2009 May;1787(5):414-20. doi: 10.1016/j.bbabio.2008.10.005. Epub 2008 Oct 25.
p53 is one of the most mutated tumor suppressors in human cancers and as such has been intensively studied for a long time. p53 is a major orchestrator of the cellular response to a broad array of stress types by regulating apoptosis, cell cycle arrest, senescence, DNA repair and genetic stability. For a long time it was thought that these functions of p53 solely rely on its function as a transcription factor, and numerous p53 target genes have been identified [1]. In the last 8 years however, a novel transcription-independent proapoptotic function mediated by the cytoplasmic pool of p53 has been revealed. p53 participates directly in the intrinsic apoptosis pathway by interacting with the multidomain members of the Bcl-2 family to induce mitochondrial outer membrane permeabilization. Our review will discuss these studies, focusing on recent advances in the field.
p53是人类癌症中突变最频繁的肿瘤抑制因子之一，因此长期以来一直受到深入研究。p53通过调节细胞凋亡、细胞周期停滞、衰老、DNA修复和遗传稳定性，在细胞对多种应激类型的反应中起主要协调作用。长期以来，人们一直认为p53的这些功能仅依赖于其作为转录因子的功能，并且已经鉴定出许多p53靶基因[1]。然而，在过去8年中，p53细胞质池介导的一种新的非转录促凋亡功能被揭示。p53通过与Bcl-2家族的多结构域成员相互作用，直接参与内源性凋亡途径，诱导线粒体外膜通透性增加。我们的综述将讨论这些研究，重点关注该领域的最新进展。
