BAP1 maintains chromosome stability by stabilizing DIDO1 in renal cell carcinoma.
Jiantao Xiao, Ruhan Zhang, Jingtao Peng, Zhonghua Yang
Abstract
gene is mutated in 5%-15% of patients with clear cell renal cell carcinoma (ccRCC), the most common form of renal cancer, which suggests that BAP1 is a tumor suppressor. However, whether BAP1 influences the progression of ccRCC tumors expressing wildtype (WT) BAP1 is unclear. Here, we identified DIDO1 as a bona fide substrate for BAP1. DIDO1 is a component of the centrosome proteins and plays an essential role in spindle assembly. BAP1 binds to DIDO1 and stabilizes DIDO1 through de-ubiquitination. BAP1 contributes to chromosome stability partially via DIDO1. A positive correlation was identified between BAP1 and DIDO1 expression in ccRCC tissues. Downregulation of both BAP1-loss and DIDO1 protein expression in ccRCC was associated with adverse clinicopathological features. This study revealed a novel mechanism involving BAP1 in the regulation of DIDO1 stability, and the results also provide insight into the relationship between BAP1 mutations and chromosome instability in ccRCC.