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

• Published in: Cell reports (Cambridge) Vol. 20; no. 3; pp. 737 - 749
• Main Authors: Li, Xu, Han, Han, Zhou, Mao-Tian, Yang, Bing, Ta, Albert Paul, Li, Nan, Chen, Junjie, Wang, Wenqi
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 18.07.2017; Elsevier
• Subjects: HEK293 Cells; Humans; peroxisome; Peroxisomes - genetics; Peroxisomes - metabolism; pexophagy; Proteomics; tankyrase; Tankyrases - genetics; Tankyrases - metabolism; pexophagy; peroxisome; proteomics; tankyrase
• ISSN: 2211-1247; 2211-1247
• DOI: 10.1016/j.celrep.2017.06.077

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. [Display omitted] •Proteomic analysis defines the human TNKS and TNKS2 protein-protein interaction network•TNKS and TNKS2 localize to peroxisomes•TNKS and TNKS2 associate with PEX14 and ATG9A and promote pexophagy Li at al. establish a protein-protein interaction network for human TNKS and TNKS2, two poly(ADP-ribose) polymerase family proteins. They examine and validate the peroxisomal localization of these tankyrases and link them to peroxisome homeostasis.