肿瘤抑制因子p53和p73的非泛素依赖性蛋白酶体降解机制。
A mechanism of ubiquitin-independent proteasomal degradation of the tumor suppressors p53 and p73.
作者信息
Asher Gad, Tsvetkov Peter, Kahana Chaim, Shaul Yosef
机构信息
Department of Molecular Genetics, Weizmann Institute of Science, Rehovot 76100, Israel.
出版信息
Genes Dev. 2005 Feb 1;19(3):316-21. doi: 10.1101/gad.319905.
Protein degradation is an essential and highly regulated process. The proteasomal degradation of the tumor suppressors p53 and p73 is regulated by both polyubiquitination and by an ubiquitin-independent process. Here, we show that this ubiquitin-independent process is mediated by the 20S proteasomes and is regulated by NQO1. NQO1 physically interacts with p53 and p73 in an NADH-dependent manner and protects them from 20S proteasomal degradation. Remarkably, the vast majority of NQO1 in cells is found in physical association with the 20S proteasomes, suggesting that NQO1 functions as a gatekeeper of the 20S proteasomes. We further show that this pathway plays a role in p53 accumulation in response to ionizing radiation. Our findings provide the first evidence for in vivo degradation of p53 and p73 by the 20S proteasomes and its regulation by NQO1 and NADH level.
蛋白质降解是一个至关重要且受到高度调控的过程。肿瘤抑制因子p53和p73的蛋白酶体降解过程既受多聚泛素化调控，也受一个不依赖泛素的过程调控。在此，我们表明这个不依赖泛素的过程由20S蛋白酶体介导，并受NQO1调控。NQO1以依赖NADH的方式与p53和p73发生物理相互作用，并保护它们免受20S蛋白酶体的降解。值得注意的是，细胞中绝大多数NQO1都与20S蛋白酶体存在物理关联，这表明NQO1作为20S蛋白酶体的守门人发挥作用。我们进一步表明，该途径在p53因电离辐射而积累的过程中发挥作用。我们的研究结果首次为20S蛋白酶体在体内对p53和p73的降解及其受NQO1和NADH水平调控提供了证据。
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