APC/C-mediated multiple monoubiquitylation provides an alternative degradation signal for cyclin B1.
APC/C-mediated multiple monoubiquitylation provides an alternative degradation signal for cyclin B1.
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DOI：
10.1038/ncb2425
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发表时间：
2012-01-29
影响因子：
21.3
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中科院分区：
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后期促进复合体/环小体（APC/C）通过泛素化细胞周期调节因子，如细胞周期蛋白B1和安全蛋白，启动有丝分裂退出。lys48连接的泛素链代表了蛋白酶体降解的典型信号靶向蛋白，但它们不是细胞周期蛋白B1降解所必需的。lys11连接的泛素链与APC/C底物的降解有关，但lys11链形成E2 UBE2S对于有丝分裂退出不是必需的，这就提出了针对APC/C底物降解的泛素信号的性质的问题。在这里，我们证明了由UBCH10或UBC4/5催化的细胞周期蛋白B1的多次单泛素化足以靶向细胞周期蛋白B1被蛋白酶体破坏。当细胞周期蛋白B1中泛素化赖氨酸的数量受到限制时，由UBE2S合成的lys11连接的泛素聚合物变得越来越重要。因此，我们解释了含有多个泛素受体位点的底物如何在调节泛素依赖性蛋白水解速率时赋予特定E2酶需求的灵活性。
The Anaphase-Promoting Complex/Cyclosome (APC/C) initiates mitotic exit by ubiquitinating cell-cycle regulators such as cyclin B1 and securin. Lys48-linked ubiquitin chains represent the canonical signal targeting proteins for degradation by the proteasome, but they are not required for the degradation of cyclin B1. Lys11-linked ubiquitin chains have been implicated in degradation of APC/C substrates, but the Lys11-chain forming E2 UBE2S is not essential for mitotic exit, raising questions about the nature of the ubiquitin signal that targets APC/C substrates for degradation. Here we demonstrate that multiple monoubiquitination of cyclin B1, catalyzed by UBCH10 or UBC4/5, is sufficient to target cyclin B1 for destruction by the proteasome. When the number of ubiquitinatable lysines in cyclin B1 is restricted, Lys11-linked ubiquitin polymers elaborated by UBE2S become increasingly important. We therefore explain how a substrate that contains multiple ubiquitin acceptor sites confers flexibility in the requirement for particular E2 enzymes in modulating the rate of ubiquitin-dependent proteolysis.
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