Research progress on the regulation of mesothelioma driven by deubiquitinating enzyme BAP1.
TL;DR
Clinical and research priorities in elucidating the signaling pathways governed by BAP1, designing targeted therapeutic strategies for BAP1-mutant cancers, and implementing preventive interventions in BAP1 mutation carriers represent urgent clinical and research priorities.
Abstract
Mesothelioma is a highly aggressive malignancy that develops through the combined influence of several factors, including environmental exposure, genetic susceptibility, immune status, and aberrant activation or dysregulation of signaling pathways. The BAP1 gene, a tumor suppressor located at chromosome 3p21.1, plays a pivotal role in maintaining genomic stability by functioning as a deubiquitinating enzyme in critical processes such as DNA damage repair, cell cycle regulation, and chromatin remodeling. Its proper activity requires nuclear localization via the nuclear localization signal (NLS) domain. When BAP1 undergoes a truncation mutation, the NLS loses its function and the protein is retained in the cytoplasm; whereas missense mutations in the UCH domain, whilst not necessarily altering subcellular localisation, can directly lead to the loss of deubiquitinase activity, thereby promoting tumour development.Consequently, elucidating the signaling pathways governed by BAP1, designing targeted therapeutic strategies for BAP1-mutant cancers, and implementing preventive interventions in BAP1 mutation carriers represent urgent clinical and research priorities.