Generation of an Interactome for the Tetratricopeptide Repeat Domain of O-GlcNAc Transferase Indicates a Role for the Enzyme in Intellectual Disability.
Generation of an Interactome for the Tetratricopeptide Repeat Domain of O-GlcNAc Transferase Indicates a Role for the Enzyme in Intellectual Disability.
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O-GlcNAc转移酶三肽重复结构域相互作用组的产生表明该酶在智力残疾中的作用。
DOI：
10.1021/acs.jproteome.0c00604
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发表时间：
2021-02-05
影响因子：
4.4
通讯作者：
Wells L
中科院分区：
文献类型：
--
作者：
Stephen HM;Praissman JL;Wells L
O-GlcNAc转移酶（OGT）用β-N-乙酰氨基葡萄糖（O-GlcNAc）修饰细胞核和细胞质蛋白。在哺乳动物基因组中编码有数千种O-GlcNAc修饰的蛋白质，但只有一种OGT，一个普遍的问题是OGT如何选择其底物。先前的工作已经表明，OGT的tetratricopeptide repeat（TPR）结构域参与底物选择。此外，导致X连锁智力残疾（XLID）的OGT的几种变体发生在TPR结构域中。因此，我们采用BioID标记方法来鉴定HeLa细胞中TPR-BirA* 融合蛋白的相互作用物。我们鉴定了115种代表已知和新型O-GlcNAc修饰蛋白和OGT相互作用物的相互作用物（原始数据保存在MassIVE中，数据集ID MSV 000085626）。相互作用物在已知的OGT过程（例如染色质重塑）以及OGT尚未涉及的过程（例如前mRNA加工）中富集。重要的是，所确定的TPR相互作用物与几种疾病状态有关，但最值得注意的是在以智力残疾为特征的病理学中富集，这可能是OGT突变导致XLID的机制的基础。OGT的TPR结构域的这种相互作用组作为未来研究的起点，探索OGT，TPR结构域及其蛋白质相互作用物在多种细胞过程和疾病机制中的作用，包括智力残疾。
The O-GlcNAc transferase (OGT) modifies nuclear and cytoplasmic proteins with β-N-Acetyl-Glucosamine (O-GlcNAc). With thousands of O-GlcNAc modified proteins but only one OGT encoded in the mammalian genome, a prevailing question is how OGT selects its substrates. Prior work has indicated that the tetratricopeptide repeat (TPR) domain of OGT is involved in substrate selection. Furthermore, several variants of OGT causal for X-linked intellectual disability (XLID) occur in the TPR domain. Therefore, we adapted the BioID labeling method to identify interactors of a TPR-BirA* fusion protein in HeLa cells. We identified 115 interactors representing known and novel O-GlcNAc modified proteins and OGT interactors (Raw data deposited in MassIVE, Dataset ID MSV000085626). The interactors are enriched in known OGT processes (e.g. chromatin remodeling) as well as processes in which OGT has yet to be implicated (e.g. pre-mRNA processing). Importantly, the identified TPR interactors are linked to several disease states but most notably are enriched in pathologies featuring intellectual disability that may underlie the mechanism by which mutations in OGT lead to XLID. This interactome for the TPR domain of OGT serves as a jumping off point for future research exploring the role of OGT, the TPR domain, and its protein interactors in multiple cellular processes and disease mechanisms, including intellectual disability.
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DOI：
10.1016/j.bbrc.2016.08.056
发表时间：
2016-09-16
影响因子：
3.1
作者：
Baldini, Steffi F.;Steenackers, Agata;Guinez, Celine
通讯作者：
Guinez, Celine
影响因子：
14.9
作者：
The Gene Ontology Consortium
通讯作者：
The Gene Ontology Consortium
影响因子：
6.7
作者：
Groussaud D;Khair M;Tollenaere AI;Waast L;Kuo MS;Mangeney M;Martella C;Fardini Y;Coste S;Souidi M;Benit L;Pique C;Issad T
通讯作者：
Issad T
通过人类蛋白质组微阵列全面鉴定 O-GlcNAc 转移酶 (OGT) 相互作用因子并构建 OGT 相互作用组
影响因子：
3.4
作者：
Deng, Rui-Ping;He, Xiang;Tao, Sheng-Ce
通讯作者：
Tao, Sheng-Ce
DOI：
10.1073/pnas.1200425109
发表时间：
2012-05-08
影响因子：
11.1
作者：
Alfaro, Joshua F.;Gong, Cheng-Xin;Smith, Richard D.
通讯作者：
Smith, Richard D.