Human kid is degraded by the APC/CCdh1 but not by the APC/CCdc20

Human kid is degraded by the APC/CCdh1 but not by the APC/CCdc20
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DOI:
10.4161/cc.6.20.4791
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发表时间:
2007-10-15
期刊:
影响因子:
4.3
通讯作者:
Brandeis, Michael
Brandeis, Michael
中科院分区:
生物学3区
文献类型:
--
作者:
Feine, Oren;Zur, Amit;Brandeis, Michael

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APC/C-Cdh 1(后期促进复合物/细胞周期小体)靶向许多细胞周期蛋白,用于有丝分裂晚期和G(1)中的泛素介导的降解。KEN盒是APC/C-Cdh 1底物的两个主要识别基序之一。然而,该基序非常常见,并且由十分之一的人类蛋白质组共享,其中绝大多数显然不是APC/C底物。我们已经观察到,大多数已知的功能性KEN盒后面是脯氨酸残基,并表明该脯氨酸在APC/C-Cdh 1特异性降解中起作用。这种见解可以用于识别新的APC/C-Cdh 1底物。我们使用该KENxP基序来鉴定人Aurora B和Kid作为APC/C-Cdh 1底物。APC/C-Cdc 20对非洲爪蟾XKid中期染色体的降解是染色体分离所必需的。相反,人Kid降解较晚,并且其APC/C-Cdh 1特异性降解不是有丝分裂进程所必需的。因此,G1中的Kid失活可能通过APC/C-Cdh 1的核螯合和降解发生。
The APC/C-Cdh1 (anaphase promoting complex/cyclosome) targets numerous cell cycle proteins for ubiquitin mediated degradation in late mitosis and G(1). The KEN box is one of two major recognition motifs of APC/C-Cdh1 substrates. This motif is however very common and shared by a tenth of the human proteome, the vast majority of which are obviously not APC/C substrates. We have observed that most known functional KEN boxes are followed by a proline residue and show that this proline plays a role in APC/C-Cdh1 specific degradation. This insight can be instrumental for identifying novel APC/C-Cdh1 substrates. We used this KENxP motif to identify human Aurora B and Kid as APC/C-Cdh1 substrates. The degradation of Xenopus XKid at metaphase by APC/C-Cdc20 is essential for chromatid segregation. Human Kid in contrast is degraded later and its APC/C-Cdh1 specific degradation is not required for mitotic progress. It is thus likely that Kid inactivation in G1 takes place both by nuclear sequestration and degradation by the APC/C-Cdh1.