RRC ID 54142
Author Li P, Huang P, Li X, Yin D, Ma Z, Wang H, Song H.
Title Tankyrase Mediates K63-Linked Ubiquitination of JNK to Confer Stress Tolerance and Influence Lifespan in Drosophila.
Journal Cell Rep
Abstract Tankyrase (Tnks) transfers poly(ADP-ribose) on substrates. Whereas studies have highlighted the pivotal roles of Tnks in cancer, cherubism, systemic sclerosis, and viral infection, the requirement for Tnks under physiological contexts remains unclear. Here, we report that the loss of Tnks or its muscle-specific knockdown impairs lifespan, stress tolerance, and energy homeostasis in adult Drosophila. We find that Tnks is a positive regulator in the JNK signaling pathway, and modest alterations in the activity of JNK signaling can strengthen or suppress the Tnks mutant phenotypes. We further identify JNK as a direct substrate of Tnks. Although Tnks-dependent poly-ADP-ribosylation is tightly coupled to proteolysis in the proteasome, we demonstrate that Tnks initiates degradation-independent ubiquitination on two lysine residues of JNK to promote its kinase activity and in vivo functions. Our study uncovers a type of posttranslational modification of Tnks substrates and provides insights into Tnks-mediated physiological roles.
Volume 25(2)
Pages 437-448
Published 2018-10-9
DOI 10.1016/j.celrep.2018.09.036
PII S2211-1247(18)31481-5
PMID 30304683
MeSH Animals Animals, Genetically Modified / genetics Animals, Genetically Modified / growth & development Animals, Genetically Modified / metabolism Drosophila Proteins / genetics Drosophila Proteins / metabolism* Drosophila melanogaster / genetics Drosophila melanogaster / growth & development* Drosophila melanogaster / metabolism Female Longevity* Lysine / chemistry* MAP Kinase Kinase 4 / genetics MAP Kinase Kinase 4 / metabolism* Male Oxidative Stress* Poly ADP Ribosylation Protein Processing, Post-Translational Proteolysis Stress, Physiological Tankyrases / genetics Tankyrases / metabolism* Ubiquitination*
IF 8.109
Times Cited 4
Drosophila 4719R-3 4719R-4