A human XPC protein interactome--a resource.
A human XPC protein interactome--a resource.
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DOI：
10.3390/ijms15010141
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发表时间：
2013-12-23
影响因子：
5.6
通讯作者：
Gong F
中科院分区：
文献类型：
--
作者：
Lubin A;Zhang L;Chen H;White VM;Gong F
全局基因组核苷酸切除修复（GG-NER）负责从非转录DNA中识别和去除由诸如UV辐射和顺铂等破坏剂引起的大体积加合物。着色性干皮病互补组C（XPC）是GG-NER途径的重要损伤识别蛋白之一，其功能障碍导致着色性干皮病（XP），这是一种涉及光敏性和癌症易感性的疾病。为了更好地了解XPC在染色质背景下对DNA损伤的鉴定以及XPC在XP发病机制中的作用，我们使用高通量酵母双杂交筛选表征了XPC的相互作用组。我们的筛选显示了49个新的XPC相互作用因子，涉及DNA修复和复制，蛋白水解和翻译后修饰，转录调节，信号转导和代谢。重要的是，我们通过co-IP验证了XPC-OTUD 4相互作用，并提供了人细胞中OTUD 4敲低确实影响泛素化XPC水平的证据，支持OTUD 4去泛素化酶通过切割泛素部分参与XPC再循环的假设。XPC相互作用组的这种高通量表征为未来的探索提供了资源，并表明XPC可能具有许多未表征的细胞功能。
Global genome nucleotide excision repair (GG-NER) is responsible for identifying and removing bulky adducts from non-transcribed DNA that result from damaging agents such as UV radiation and cisplatin. Xeroderma pigmentosum complementation group C (XPC) is one of the essential damage recognition proteins of the GG-NER pathway and its dysfunction results in xeroderma pigmentosum (XP), a disorder involving photosensitivity and a predisposition to cancer. To better understand the identification of DNA damage by XPC in the context of chromatin and the role of XPC in the pathogenesis of XP, we characterized the interactome of XPC using a high throughput yeast two-hybrid screening. Our screening showed 49 novel interactors of XPC involved in DNA repair and replication, proteolysis and post-translational modifications, transcription regulation, signal transduction, and metabolism. Importantly, we validated the XPC-OTUD4 interaction by co-IP and provided evidence that OTUD4 knockdown in human cells indeed affects the levels of ubiquitinated XPC, supporting a hypothesis that the OTUD4 deubiquitinase is involved in XPC recycling by cleaving the ubiquitin moiety. This high-throughput characterization of the XPC interactome provides a resource for future exploration and suggests that XPC may have many uncharacterized cellular functions.
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影响因子：
64.5
作者：
Fong YW;Inouye C;Yamaguchi T;Cattoglio C;Grubisic I;Tjian R
通讯作者：
Tjian R
影响因子：
3.7
作者：
Fu M;Rao R;Sudhakar D;Hogue CP;Rutta Z;Morales S;Gordon LK;Braun J;Goodglick L;Wadehra M
通讯作者：
Wadehra M
影响因子：
4.8
作者：
Araki, M;Masutani, C;Hanaoka, F
通讯作者：
Hanaoka, F
影响因子：
4.8
作者：
Forbes, Ashley;Wadehra, Madhuri;Braun, Jonathan
通讯作者：
Braun, Jonathan
影响因子：
7
作者：
Lehner, B;Sanderson, CM
通讯作者：
Sanderson, CM