{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T23:38:21Z","timestamp":1789601901270,"version":"build-2803163510"},"reference-count":38,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2022,6,7]],"date-time":"2022-06-07T00:00:00Z","timestamp":1654560000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIP)","award":["NRF-2016R1A2B4008830"],"award-info":[{"award-number":["NRF-2016R1A2B4008830"]}]},{"name":"National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIP)","award":["NRF-2019R1A6A1A03032888"],"award-info":[{"award-number":["NRF-2019R1A6A1A03032888"]}]},{"name":"Basic Research Program through the National Research Foundation of Korea (NRF) funded by the ministry of Education","award":["NRF-2016R1A2B4008830"],"award-info":[{"award-number":["NRF-2016R1A2B4008830"]}]},{"name":"Basic Research Program through the National Research Foundation of Korea (NRF) funded by the ministry of Education","award":["NRF-2019R1A6A1A03032888"],"award-info":[{"award-number":["NRF-2019R1A6A1A03032888"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The CDC73\/HRPT2 gene, a defect which causes hyperparathyroidism\u2013jaw tumor (HPT-JT) syndrome, encodes CDC73\/parafibromin. We aimed to investigate whether CDC73 would be a target for ubiquitin\u2013proteasome degradation. We cloned full-length cDNAs encoding a family of 58 ubiquitin-specific deubiquitinating enzymes (DUBs), also known as ubiquitin-specific proteases (USPs). Use of the yeast two-hybrid system then enabled us to identify USP37 as interacting with CDC73. The biochemical interaction between the USP37 and CDC73 and their reciprocal binding domains were studied. Co-localization of CDC73 and USP37 was observed in cells. CDC73 was found to be polyubiquitinated, and polyubiquitination of CDC73 was prominent in mutants. CDC73 was deubiquitinated via K48-specific ubiquitin chains by USP37, but not by the catalytically inactive USP37C350S mutant. Observation of the binding between deletion mutants of CDC73 and USP37 revealed that the \u03b2-catenin binding site of CDC73 and the ubiquitin-interacting motifs 2 and 3 (UIM2 and 3) of USP37 were responsible for the interaction between the two proteins. Moreover, these two enzymes co-existed within the nucleus of COS7 cells. We conclude that USP37 is a DUB for CDC73 and that the two proteins interact through specific domains, suggesting that USP37 is responsible for the stability of CDC73 in HPT-JT syndrome.<\/jats:p>","DOI":"10.3390\/ijms23126364","type":"journal-article","created":{"date-parts":[[2022,6,10]],"date-time":"2022-06-10T02:25:33Z","timestamp":1654827933000},"page":"6364","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["USP37 Deubiquitinates CDC73 in HPT-JT Syndrome"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6908-3890","authenticated-orcid":false,"given":"Su Yeon","family":"Kim","sequence":"first","affiliation":[{"name":"Institute of Biomedical Industry, College of Medicine, The Catholic University of Korea, Seoul 06591, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ji-young","family":"Lee","sequence":"additional","affiliation":[{"name":"Institute of Biomedical Industry, College of Medicine, The Catholic University of Korea, Seoul 06591, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9940-1909","authenticated-orcid":false,"given":"Yun-jung","family":"Cho","sequence":"additional","affiliation":[{"name":"Division of Endocrinology and Metabolism, Department of Internal Medicine, Incheon St. Mary\u2019s Hospital, College of Medicine, The Catholic University of Korea, Incheon 21431, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kwan Hoon","family":"Jo","sequence":"additional","affiliation":[{"name":"Division of Endocrinology and Metabolism, Department of Internal Medicine, Incheon St. Mary\u2019s Hospital, College of Medicine, The Catholic University of Korea, Incheon 21431, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eun Sook","family":"Kim","sequence":"additional","affiliation":[{"name":"Division of Endocrinology and Metabolism, Department of Internal Medicine, Incheon St. Mary\u2019s Hospital, College of Medicine, The Catholic University of Korea, Incheon 21431, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Je Ho","family":"Han","sequence":"additional","affiliation":[{"name":"Division of Endocrinology and Metabolism, Department of Internal Medicine, Incheon St. Mary\u2019s Hospital, College of Medicine, The Catholic University of Korea, Incheon 21431, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7662-7190","authenticated-orcid":false,"given":"Kwang-Hyun","family":"Baek","sequence":"additional","affiliation":[{"name":"Department of Biomedical Science, CHA University, Seongnam 13488, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3094-9415","authenticated-orcid":false,"given":"Sung-dae","family":"Moon","sequence":"additional","affiliation":[{"name":"Institute of Biomedical Industry, College of Medicine, The Catholic University of Korea, Seoul 06591, Korea"},{"name":"Division of Endocrinology and Metabolism, Department of Internal Medicine, Incheon St. Mary\u2019s Hospital, College of Medicine, The Catholic University of Korea, Incheon 21431, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,6,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"15638","DOI":"10.1038\/s41598-017-15715-9","article-title":"Crystal structure of the N-terminal domain of human CDC73 and its implications for the hyperparathyroidism-jaw tumor (HPT-JT) syndrome","volume":"7","author":"Sun","year":"2017","journal-title":"Sci. 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