O-GlcNAcylation Prevents Aggregation of the Polycomb Group Repressor Polyhomeotic
O-GlcNAcylation Prevents Aggregation of the Polycomb Group Repressor Polyhomeotic
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DOI：
10.1016/j.devcel.2014.10.020
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发表时间：
2014-12-01
影响因子：
11.8
通讯作者：
Mueller, Juerg
中科院分区：
文献类型：
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作者：
Gambetta, Maria Cristina;Mueller, Juerg
糖基转移酶Ogt将O-连接的N-乙酰葡糖胺（O-GlcNAc）部分添加到核和胞质蛋白中。果蝇胚胎缺乏Ogt蛋白逮捕发展与一个非常具体的Polycomb表型，由于未能抑制Polycomb靶基因。Polycomb蛋白Polyhomeotic（Ph）是一种Ogt底物，在体内和体外不存在O-GlcNAcylation的情况下形成大聚集体。Ph中丝氨酸/苏氨酸（SIT）片段的O-GlcNAc化对于防止果蝇和人Ph通过其C-末端无菌α基序（SAM）结构域在体外的非生产性聚集至关重要。体内完整的Ph阻遏物活性需要SAM结构域和SIT段的O-GlcNAc化。我们证明，Ph突变体缺乏SIT拉伸复制ogt突变体的表型，这表明在Ph的S/T拉伸是关键的Ogt基板在果蝇。我们建议，O-GlcNAc酰化是需要的Ph形成功能，通过其SAM结构域的有序组件。
The glycosyltransferase Ogt adds O-linked N-Acetylglucosamine (O-GlcNAc) moieties to nuclear and cytosolic proteins. Drosophila embryos lacking Ogt protein arrest development with a remarkably specific Polycomb phenotype, arising from the failure to repress Polycomb target genes. The Polycomb protein Polyhomeotic (Ph), an Ogt substrate, forms large aggregates in the absence of O-GlcNAcylation both in vivo and in vitro. O-GlcNAcylation of a serine/threonine (SIT) stretch in Ph is critical to prevent nonproductive aggregation of both Drosophila and human Ph via their C-terminal sterile alpha motif (SAM) domains in vitro. Full Ph repressor activity in vivo requires both the SAM domain and O-GlcNAcylation of the SIT stretch. We demonstrate that Ph mutants lacking the SIT stretch reproduce the phenotype of ogt mutants, suggesting that the S/T stretch in Ph is the key Ogt substrate in Drosophila. We propose that O-GlcNAcylation is needed for Ph to form functional, ordered assemblies via its SAM domain.