Proteomic Analysis of the Human Tankyrase Protein Interaction Network Reveals Its Role in Pexophagy
Proteomic Analysis of the Human Tankyrase Protein Interaction Network Reveals Its Role in Pexophagy
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DOI：
10.1016/j.celrep.2017.06.077
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发表时间：
2017-07-18
期刊：
影响因子：
8.8
通讯作者：
Wang, Wenqi
中科院分区：
文献类型：
--
作者：
Li, Xu;Han, Han;Wang, Wenqi
端锚聚合酶1（TNKS）和端锚聚合酶2（TNKS 2）属于聚（ADP-核糖）聚合酶蛋白家族，其使用烟酰胺腺嘌呤二核苷酸来修饰具有ADP-核糖修饰的底物蛋白。新出现的证据揭示了TNKS和TNKS 2的病理相关性，并将这两种酶确定为潜在的药物靶点。然而，TNKS/2的细胞功能和调节机制在很大程度上仍然未知。通过蛋白质组学分析，我们定义了人类TNKS/2的蛋白质-蛋白质相互作用网络，并在该网络中揭示了100多个具有多种生物学功能的高置信度相互作用蛋白。最后，通过功能验证，我们发现了TNKS/2在过氧化物酶体内平衡中的作用，并确定该功能独立于TNKS酶活性。我们对TNKS/2蛋白相互作用网络的蛋白质组学研究为进一步探索许多细胞过程中的端锚聚合酶功能提供了丰富的资源。
Tankyrase 1 (TNKS) and tankyrase 2 (TNKS2) belong to the poly(ADP-ribose) polymerase family of proteins, which use nicotinamide adenine dinucleotide to modify substrate proteins with ADP-ribose modifications. Emerging evidence has revealed the pathological relevance of TNKS and TNKS2, and identified these two enzymes as potential drug targets. However, the cellular functions and regulatory mechanisms of TNKS/2 are still largely unknown. Through a proteomic analysis, we defined the protein-protein interaction network for human TNKS/2 and revealed more than 100 high-confidence interacting proteins with numerous biological functions in this network. Finally, through functional validation, we uncovered a role for TNKS/2 in peroxisome homeostasis and determined that this function is independent of TNKS enzyme activities. Our proteomic study of the TNKS/2 protein interaction network provides a rich resource for further exploration of tankyrase functions in numerous cellular processes.