Moll U M, Zaika A
Department of Pathology, State University of New York at Stony Brook, 11794, Stony Brook, NY, USA.
FEBS Lett. 2001 Mar 30;493(2-3):65-9. doi: 10.1016/s0014-5793(01)02284-0.
In contrast to p53-mediated cell cycle arrest, the mechanisms of p53-mediated apoptosis in response to cellular stresses such as DNA damage, hypoxia and oncogenic signals still remain poorly understood. Elucidating these pathways is all the more pressing since there is good evidence that the activation of apoptosis rather than cell cycle arrest is crucial in p53 tumor suppression. Moreover, the therapeutic interest in p53 as the molecular target of anticancer intervention rests mainly on its powerful apoptotic capability. This puzzling elusiveness suggests that p53 not only engages a plethora of downstream pathways but itself might possess a biochemical flexibility that goes beyond its role as a mere transcription factor. Recent evidence of a direct pro-apoptotic role of p53 protein at mitochondria suggests a synergistic effect with its transcriptional activation function and brings an unexpected new level of complexity into p53 apoptotic pathways.
与p53介导的细胞周期停滞不同，p53在应对诸如DNA损伤、缺氧和致癌信号等细胞应激时介导细胞凋亡的机制仍知之甚少。鉴于有充分证据表明凋亡而非细胞周期停滞的激活在p53肿瘤抑制中至关重要，阐明这些途径就显得更加紧迫。此外，将p53作为抗癌干预分子靶点的治疗意义主要在于其强大的凋亡能力。这种令人费解的难以捉摸表明，p53不仅涉及众多下游途径，而且其本身可能具有超越其作为单纯转录因子角色的生化灵活性。最近有证据表明p53蛋白在线粒体上具有直接的促凋亡作用，这表明它与其转录激活功能具有协同效应，并给p53凋亡途径带来了意想不到的新的复杂程度。
