Tankyrase-1 assembly to large protein complexes blocks its telomeric function |
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Authors: | Kaori Hatsugai Tomokazu Ohishi Hiroyuki Seimiya |
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Affiliation: | a Division of Molecular Biotherapy, Cancer Chemotherapy Center, Japanese Foundation for Cancer Research, 3-8-31 Ariake, Koto-ku, Tokyo 135-8550, Japan b Division of Chemotherapy, Faculty of Pharmacy, Keio University, 1-5-30 Shiba-Koen, Minato-ku, Tokyo 105-8512, Japan c Division of Gene Therapy, Cancer Chemotherapy Center, Japanese Foundation for Cancer Research, 3-8-31 Ariake, Koto-ku, Tokyo 135-8550, Japan |
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Abstract: | 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.Structured summaryMINT-7987689, MINT-7987677: Tankyrase-1 (uniprotkb:O95271) and TRF1 (uniprotkb:P54274) colocalize (MI:0403) by fluorescence microscopy (MI:0416)MINT-7987977: Tankyrase-1 (uniprotkb:O95271) physically interacts (MI:0915) with TRF1 (uniprotkb:P54274) by anti tag coimmunoprecipitation (MI:0007)MINT-7987998: Tankyrase-1 (uniprotkb:O95271) physically interacts (MI:0915) with Tankyrase-1 (uniprotkb:O95271) by anti tag coimmunoprecipitation (MI:0007). |
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Keywords: | 3AB, 3-aminobenzamide ARC, ankyrin repeat cluster FN, FLAG tag and nuclear localization signal HDAC, histone deacetylase PARP, poly(ADP-ribose) polymerase PARsylation, poly(ADP-ribosyl)ation SAM, sterile alpha motif TRF1, telomeric repeat-binding factor 1 TSA, trichostatin A VPA, valproic acid |
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