A role for non-covalent SUMO interaction motifs in Pc2/CBX4 E3 activity.
A role for non-covalent SUMO interaction motifs in Pc2/CBX4 E3 activity.
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DOI：
10.1371/journal.pone.0008794
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发表时间：
2010-01-20
期刊：
影响因子：
3.7
通讯作者：
Wotton D
中科院分区：
文献类型：
--
作者：
Merrill JC;Melhuish TA;Kagey MH;Yang SH;Sharrocks AD;Wotton D
小泛素样修饰物（SUMO）对蛋白质的修饰是哺乳动物细胞中的一个重要过程。SUMO通过由E1和E2、SUMO激活酶和缀合酶组成的酶级联反应共价连接到靶蛋白的赖氨酸上。对于非酶促E3衔接子样蛋白也存在可变的需求，其可以增加类小泛素化过程的效率和特异性。除了SUMO与靶蛋白的共价连接之外，已经鉴定了通常是短疏水肽基序的特异性非共价SUMO相互作用基序（西姆斯）。有趣的是，大多数SUMO E3中都存在共有西姆斯，包括多梳蛋白Pc 2/Cbx 4。然而，西姆斯在SUMO E3活动中的作用仍有待证实。我们发现Pc 2包含两个功能西姆斯，这两个SIM都有助于哺乳动物细胞中的完整E3活性，并且也是Pc 2本身的类苏修饰所需的。Pc 2形成独特的亚核灶，称为多梳体，并可以招募伴侣蛋白，如辅阻遏物CtBP。我们证明，突变的西姆斯在Pc 2阻止Pc 2依赖的CtBP类小泛素化，并减少富集的SUMO 1和SUMO 2在polycomb灶。此外，SUMO 1和SUMO 2的突变分析表明，这两个SUMO亚型的SIM相互作用的残基所需的Pc 2介导的类小泛素化和本地化的polycomb灶。这项工作为西姆斯在SUMO E3活动中的作用提供了首次明确的证据。
Modification of proteins by the small ubiquitin like modifier (SUMO) is an essential process in mammalian cells. SUMO is covalently attached to lysines in target proteins via an enzymatic cascade which consists of E1 and E2, SUMO activating and conjugating enzymes. There is also a variable requirement for non-enzymatic E3 adapter like proteins, which can increase the efficiency and specificity of the sumoylation process. In addition to covalent attachment of SUMO to target proteins, specific non-covalent SUMO interaction motifs (SIMs) that are generally short hydrophobic peptide motifs have been identified. Intriguingly, consensus SIMs are present in most SUMO E3s, including the polycomb protein, Pc2/Cbx4. However, a role for SIMs in SUMO E3 activity remains to be shown. We show that Pc2 contains two functional SIMs, both of which contribute to full E3 activity in mammalian cells, and are also required for sumoylation of Pc2 itself. Pc2 forms distinct sub-nuclear foci, termed polycomb bodies, and can recruit partner proteins, such as the corepressor CtBP. We demonstrate that mutation of the SIMs in Pc2 prevents Pc2-dependent CtBP sumoylation, and decreases enrichment of SUMO1 and SUMO2 at polycomb foci. Furthermore, mutational analysis of both SUMO1 and SUMO2 reveals that the SIM-interacting residues of both SUMO isoforms are required for Pc2-mediated sumoylation and localization to polycomb foci. This work provides the first clear evidence for a role for SIMs in SUMO E3 activity.
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