ECE2019 Guided Posters Adrenal and Neuroendocrine - Tumour (14 abstracts)
Parafibromin is regulated by ubiquitin specific protease 37 (USP37) and the c-terminus of USP37 interacts with the beta-catenin binding region of CDC73 in hyperparathyroidism-jaw tumor syndrome
Su Yeon Kim 1 , Ji-young Lee 1 , Kwan Hoon Jo 1 , Eun Yeong Mo 1 , Eun Sook Kim 1 , Je Ho Han 1 & Kwang-Hyun Baek 2
1Department of Internal Medicine, Incheon St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea; 2Department of Biomedical Science, CHA University, Pocheon, Republic of Korea.
CDC73 (also known as HRPT2) encodes parafibromin and is known to be the causative gene of hyperparathyroidism-jaw tumor (HPT-JT) syndrome. There is no known ubiquitination of parafibromin, and the deubiquitinating enzyme (DUB) for parafibromin has not been identified to date. Full-length DUB cDNAs encoding 58 family members of ubiquitin specific proteases (USPs) were subcloned. The DUB cDNA was used to identify parafibromin interacting by yeast two-hybrid screening. We investigated biochemical interactions between specific DUBs and parafibromin to confirm their binding and to investigate whether specific DUBs deconjugate ubiquitin from parafibromin by GST pull-down and immunoprecipitation analysis, respectively. And we examined the binding region of USP37 and parafibromin, and vice versa. Parafibromin was polyubiquitinated, especially in mutant forms. In yeast two-hybrid assays, USP37 was found to be a DUB interacting with parafibromin. GST pull-down analysis confirmed that parafibromin binds to USP37. We have shown that parafibromin can bind directly to USP37 and have demonstrated that USP37 specifically controls K48-linked polyubiquitination and stabilizes parafibromin. To determine the correct binding site, full length and deletion constructs were generated for both USP37 and CDC73. Simultaneous immunoprecipitation analysis betweenthe USP37 full length and CDC73 deletion constructs and the CDC73 full length and USP deletion constructs was performed. The analysis revealed that the c-terminus of USP37 interacted with the beta-catenin binding region of CDC73. Our results suggest that USP37 is a novel regulator of parafibromin stability in HPT-JT syndrome.
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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