Proteasomal turnover of p21Cip1 does not require p21Cip1 ubiquitination
Proteasomal turnover of p21Cip1 does not require p21Cip1 ubiquitination
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DOI：
10.1016/s1097-2765(00)80435-9
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发表时间：
2000-02-01
期刊：
影响因子：
16
通讯作者：
Clurman, BE
中科院分区：
文献类型：
--
作者：
Sheaff, RJ;Singer, JD;Clurman, BE
Cdk 抑制剂 p21(Cip1) 是一种不稳定的蛋白质。蛋白酶体的药理抑制将 p21 的半衰期从不到 30 分钟延长至 2 小时以上，并导致 p21-泛素缀合物的积累。为了确定 p21 的蛋白酶体降解是否需要泛素化，我们构建了体内未泛素化的 p21 突变体版本。值得注意的是，这些突变体在蛋白酶体抑制后保持不稳定并丰度增加，表明 p21 的直接泛素化对于蛋白酶体的周转来说并不是必需的。经常观察到的蛋白质泛素化与蛋白酶体降解之间的相关性不足以得出泛素化是降解的先决条件的结论。
The Cdk inhibitor p21(Cip1) is an unstable protein. Pharmacologic inhibition of the proteasome increases the half-life of p21 from less than 30 min to more than 2 hr and results in the accumulation of p21-ubiquitin conjugates. To determine whether ubiquitination was required for proteasomal degradation of p21, we constructed mutant versions of p21 that were not ubiquitinated in vivo. Remarkably, these mutants remained unstable and increased in abundance upon proteasome inhibition, indicating that direct ubiquitination of p21 is not necessary for its turnover by the proteasome. The frequently observed correlation between protein ubiquitination and proteasomal degradation is insufficient to conclude that ubiquitination is a prerequisite for degradation.