CR-UK Beatson Institute, Garscube Estate, Switchback Road, Glasgow G61 1BD, UK.
Mol Cell. 2013 Jun 27;50(6):805-17. doi: 10.1016/j.molcel.2013.05.002. Epub 2013 Jun 6.
p53 is a transcription factor that mediates tumor suppressor responses. Correct folding of the p53 protein is essential for these activities, and point mutations that induce conformational instability of p53 are frequently found in cancers. These mutant p53s not only lose wild-type activity but can also acquire the ability to promote invasion and metastasis. We show that folding of wild-type p53 is promoted by an interaction with the chaperonin CCT. Depletion of this chaperone in cells results in the accumulation of misfolded p53, leading to a reduction in p53-dependent gene expression. Intriguingly, p53 proteins mutated to prevent the interaction with CCT show conformational instability and acquire an ability to promote invasion and random motility that is similar to the activity of tumor-derived p53 mutants. Our data therefore suggest that both growth suppression and cell invasion may be differentially regulated functions of wild-type p53.
p53 是一种转录因子，介导肿瘤抑制应答。p53 蛋白的正确折叠对于这些活性至关重要，并且在癌症中经常发现诱导 p53 构象不稳定的点突变。这些突变的 p53 不仅失去野生型活性，而且还可以获得促进侵袭和转移的能力。我们表明，野生型 p53 的折叠通过与伴侣蛋白 CCT 的相互作用而得到促进。细胞中这种伴侣蛋白的耗竭会导致错误折叠的 p53 积累，从而导致 p53 依赖性基因表达减少。有趣的是，突变以防止与 CCT 相互作用的 p53 蛋白显示构象不稳定，并获得类似于肿瘤衍生的 p53 突变体的促进侵袭和随机运动的能力。因此，我们的数据表明，生长抑制和细胞侵袭可能是野生型 p53 的不同调节功能。
