The mitochondrial p53 pathway.

The mitochondrial p53 pathway.
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DOI:
10.1016/j.bbabio.2008.10.005
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发表时间:
2009-05
影响因子:
4.3
通讯作者:
Moll, Ute M.
Moll, Ute M.
中科院分区:
生物学2区
文献类型:
--
作者:
Vaseva, Angelina V.;Moll, Ute M.

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p53 是人类癌症中突变最严重的肿瘤抑制因子之一,因此已被深入研究了很长时间。 p53 是细胞对多种应激类型反应的主要协调者,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。长期以来,人们认为p53的这些功能仅依赖于其作为转录因子的功能,并且已经鉴定了许多p53靶基因。然而,在过去的 8 年里,由 p53 细胞质池介导的一种新的不依赖于转录的促凋亡功能被揭示。 p53 通过与 Bcl-2 家族的多结构域成员相互作用诱导线粒体外膜通透,直接参与内在凋亡途径。我们的评论将讨论这些研究,重点关注该领域的最新进展。
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. 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.
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