Pd46-01 bap1 de-ubiquitinase is allosterically regulated by asxl1/2: somatic bap1 mutation in rcc and other tumors inactive this regulation by targeting multiple independent domains

BAP1 is a ubiquitin carboxy-terminal hydrolase enzyme (UCH) which along with the ASXL1/2 protein forms the PR-DUB, chromatin associated complex which removes monoubiquitin from H2A in nucleosomes regulating gene expression. BAP1 is a tumor suppressor gene commonly mutated gene in clear cell renal cell carcinoma (ccRCC) and other cancers such as uveal melanoma (UM) and mesothelioma. In tumors, BAP1 mutations occur throughout the protein well outside the N-terminal UCH catalytic region while C-terminal BAP1 truncations/mutations in the ULD domain also inactivate BAP.

Source: The Journal of Urology - April 1, 2018 Category: Urology & Nephrology Authors: Hongzhuang Peng, Jeremy Prokop, Jayashree Karar, Kyewon Park, S. Bruce Malkowicz, Li Cao, J. William Harbour, Anne Bowcock, Mitchell Cheung, Joesph A Testa, Frank J Rauscher Tags: Kidney Cancer: Basic Research & Pathophysiology I Source Type: research