Chipuk Jerry E, Green Douglas R
Division of Cellular Immunology, La Jolla Institute for Allergy and Immunology, 10355 Science Center Drive, San Diego, California 92121, USA.
J Clin Immunol. 2003 Sep;23(5):355-61. doi: 10.1023/a:1025365432325.
The requirement for an intact p53 signaling pathway to sense tumor-promoting DNA damage is evident from over 20 years of molecular, cellular, and whole animal studies. Without a doubt, p53's major contribution in maintaining the genomic integrity of multicellular organisms is through transcriptional regulation of genes required for cell cycle arrest, DNA repair, and apoptosis. Nonetheless, evidence is mounting that p53 has an extranuclear role in the cytoplasm to induce apoptosis, perhaps coupled to its transcriptional effects, or conceivably at instances when transcription is not optimal or possible. This phenomenon, transcription-independent p53-induced apoptosis (TIPA), has been described for almost 10 years, yet little is known about mechanisms by which p53 can directly engage the apoptotic cascade in the absence of transcription. Here we will explore what is currently known about TIPA learned from various p53 mutants and truncations, along with discussing several proposed mechanisms.
二十多年来的分子、细胞和整体动物研究表明，完整的p53信号通路对于感知促肿瘤DNA损伤是必需的。毫无疑问，p53在维持多细胞生物体基因组完整性方面的主要贡献是通过对细胞周期停滞、DNA修复和凋亡所需基因的转录调控来实现的。尽管如此，越来越多的证据表明，p53在细胞质中具有核外作用以诱导凋亡，这可能与其转录效应相关，或者可以想象在转录不理想或不可能的情况下也是如此。这种现象，即不依赖转录的p53诱导凋亡（TIPA），已经被描述了近十年，但对于p53在没有转录的情况下能够直接参与凋亡级联反应的机制却知之甚少。在这里，我们将探讨从各种p53突变体和截短体中了解到的关于TIPA的当前知识，并讨论几种提出的机制。
