Tankyrase-1 assembly to large protein complexes blocks its telomeric function.
Tankyrase-1 poly(ADP-ribosyl)ates the telomere-binding protein TRF1. This post-translational modification dissociates TRF1 from telomeres, enhancing telomerase-mediated telomere elongation. Tankyrase-1 multimerizes via its sterile alpha motif domain, but its functional implication remains elusive. Here, we found that excessive amounts of tankyrase-1 form punctate nuclear foci. This focus formation depends on both homophilic multimerization and heterophilic protein-protein interaction. These foci are functionally dormant because they do not efficiently release TRF1 from telomeres. Consistently, hyper-overexpression of tankyrase-1 attenuates its ability to elongate telomeres. These observations suggest that tankyrase-1 assembly to large protein complexes masks its telomeric function.
Hatsugai
Kaori
K
Division of Molecular Biotherapy, Cancer Chemotherapy Center, Japanese Foundation for Cancer Research, Tokyo, Japan.
Ohishi
Tomokazu
T
Sugimoto
Yoshikazu
Y
Seimiya
Hiroyuki
H
D015870:Gene Expression / Q000187:drug effects; D006367:HeLa Cells; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology; D006801:Humans; D047468:Immunoprecipitation; D009097:Multienzyme Complexes / Q000235:genetics / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D017434:Protein Structure, Tertiary; D038501:Tankyrases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D016615:Telomere / Q000201:enzymology* / Q000502:physiology
D056572:Histone Deacetylase Inhibitors; D009097:Multienzyme Complexes; D038501:Tankyrases; C418109:TNKS protein, human