人类 Tankyrase 蛋白相互作用网络的蛋白质组学分析揭示了其在 Pexophagy 中的作用。

Proteomic Analysis of the Human Tankyrase Protein Interaction Network Reveals Its Role in Pexophagy.

机构信息

Department of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.

Department of Developmental and Cell Biology, University of California, Irvine, Irvine, CA 92697, USA.

出版信息

Cell Rep. 2017 Jul 18;20(3):737-749. doi: 10.1016/j.celrep.2017.06.077.

DOI:10.1016/j.celrep.2017.06.077

PMID:28723574

Abstract

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.

摘要

Tankyrase 1 (TNKS) 和 tankyrase 2 (TNKS2) 属于聚（ADP-核糖）聚合酶家族蛋白，它们利用烟酰胺腺嘌呤二核苷酸将 ADP-核糖修饰物修饰到底物蛋白上。新出现的证据揭示了 TNKS 和 TNKS2 的病理学相关性，并将这两种酶鉴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可信度相互作用蛋白。最后，通过功能验证，我们揭示了 TNKS/2 在过氧化物酶体动态平衡中的作用，并确定了这一功能独立于 TNKS 酶活性。我们对 TNKS/2 蛋白质相互作用网络的蛋白质组学研究为进一步探索 tankyrase 在众多细胞过程中的功能提供了丰富的资源。