Ubiquitylation of the amino terminus of Myc by SCFβ-TrCP antagonizes SCFFbw7-mediated turnover
Ubiquitylation of the amino terminus of Myc by SCFβ-TrCP antagonizes SCFFbw7-mediated turnover
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DOI：
10.1038/ncb2104
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发表时间：
2010-10-01
影响因子：
21.3
通讯作者：
Eilers, Martin
中科院分区：
文献类型：
--
作者：
Popov, Nikita;Schuelein, Christina;Eilers, Martin
SCFFbw 7泛素连接酶介导生长因子调节的Myc癌蛋白周转。在这里，我们发现SCF β-TrCP通过特征性的磷酸降解决定子与Myc结合，并使Myc泛素化;这导致Myc稳定性增强。SCFFbw 7和SCF beta-TrCP可以通过Myc氨基末端的多泛素化来发挥这些差异效应。而具有Cdc 34泛素缀合酶的SCFFbw 7特异性地需要泛素的赖氨酸48（K48），SCF beta-TrCP使用UbcH 5泛素缀合酶在Myc上形成异型聚泛素链。SCF β-TrCP对Myc的泛素化是Myc依赖性加速细胞周期进程所必需的，在S期停滞释放后。因此，在N末端的替代泛素化事件可以导致Myc的泛素化依赖性稳定。
The SCFFbw7 ubiquitin ligase mediates growth-factor-regulated turnover of the Myc oncoprotein. Here we show that SCF beta-TrCP binds to Myc by means of a characteristic phosphodegron and ubiquitylates Myc; this results in enhanced Myc stability. SCFFbw7 and SCF beta-TrCP can exert these differential effects through polyubiquitylation of the amino terminus of Myc. Whereas SCFFbw7 with the Cdc34 ubiquitin-conjugating enzyme specifically requires lysine 48 (K48) of ubiquitin, SCF beta-TrCP uses the UbcH5 ubiquitin-conjugating enzyme to form heterotypic polyubiquitin chains on Myc. Ubiquitylation of Myc by SCF beta-TrCP is required for Myc-dependent acceleration of cell cycle progression after release from an arrest in S phase. Therefore, alternative ubiquitylation events at the N terminus can lead to the ubiquitylation-dependent stabilization of Myc.