Ubiquitin-independent degradation of cell-cycle inhibitors by the REGγ proteasome
Ubiquitin-independent degradation of cell-cycle inhibitors by the REGγ proteasome
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DOI：
10.1016/j.molcel.2007.05.022
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发表时间：
2007-06-22
期刊：
影响因子：
16
通讯作者：
Roberts, James M.
中科院分区：
文献类型：
--
作者：
Chen, Xueyan;Barton, Lance F.;Roberts, James M.
细胞周期调节因子p21（Cip 1）被蛋白酶体降解，不依赖于泛素化。我们现在表明，p21在体内的降解不需要19 S蛋白酶体盖，其中包含的泛素结合亚基。相反，p21降解的主要蛋白酶体途径涉及替代蛋白酶体盖，REG γ复合物。REG γ在体内与p21结合，并且p21的REG γ结合位点的缺失极大地延长了其半衰期。通过RNA干扰敲低REG γ稳定p21，p21在REG γ（-/-）鼠胚胎成纤维细胞中具有显著延长的半衰期，并且p21丰度在REG γ（-/-）小鼠中升高。REG γ在细胞周期调控中的作用可能超出p21调控，因为p16（INK 4A）和p19（Arf）也与REG γ结合，并在REG γ缺陷细胞中稳定。
The cell-cycle regulator p21(Cip1) is degraded by proteasomes independently of ubiquitination. We now show that degradation of p21 in vivo does not require the 19S proteasome lid, which contains the ubiquitin-binding subunit. Instead, the major proteasomal pathway for p21 degradation involves an alternative proteasome lid, the REG gamma complex. REG gamma binds to p21 in vivo, and deletion of p21's REG gamma-binding site greatly extends its half-life. Knockdown of REG gamma by RNA interference stabilizes p21, p21 has a significantly extended half-life in REG gamma(-/-) murine embryonic fibroblasts, and the p21 abundance is elevated in REG gamma(-/-) mice. The role of REG gamma in cell-cycle regulation may extend beyond p21 regulation, because p16(INK4A) and p19(Arf) also bind to REG gamma and are stabilized in REG gamma-deficient cells.