Bap1-KO Mouse

BAP1, short for BRCA1-Associated Protein 1, is a ubiquitin carboxy-terminal hydrolase. As a tumor suppressor, it uses its deubiquitinating activity to regulate multiple processes like DNA damage repair, cell cycle control, chromatin modification, programmed cell death, and the immune response [1,3,5]. It is also involved in metabolic regulation of ferroptosis [2].

In CRISPR-engineered human cholangiocyte organoids, BAP1 loss-of-function led to loss of epithelial characteristics and increased motility, and restoring its catalytic activity in the nucleus rescued these changes. In human liver organoids with combined common cholangiocarcinoma mutations, BAP1 loss resulted in acquisition of malignant features upon xenotransplantation, suggesting that BAP1 controls epithelial identity through chromatin accessibility regulation [4].

In conclusion, BAP1 is crucial in maintaining normal cellular functions, especially in processes related to tumor suppression. Its role in regulating epithelial identity and involvement in various cancer-related processes, such as in cholangiocarcinoma, are well-demonstrated through organoid-based functional studies. These findings enhance our understanding of BAP1's function and its implications in cancer development and treatment.