Bub1b-flox Mouse

BUB1b, also known as BUB1 mitotic checkpoint serine/threonine kinase B, is a crucial gene involved in the mitotic spindle assembly checkpoint. It plays a key role in ensuring accurate chromosome segregation during cell division, which is essential for maintaining genomic stability. Dysregulation of BUB1b can lead to chromosomal instability, a hallmark of many cancers [3,4].

In multiple cancers, loss-of-function assays have revealed its oncogenic role. In lung adenocarcinoma, knockdown of BUB1b reduced cell viability, and it was found to enhance resistance to ferroptosis and chemotherapy by stabilizing the NRF2 signaling pathway through forming a complex with OTUD3 and NRF2 [1]. In extrahepatic cholangiocarcinoma, inhibition of BUB1b decreased cell proliferation and invasiveness both in vitro and in vivo, and it was shown to act via the JNK/c-Jun pathways [2]. Similar results were seen in multiple myeloma, where targeting BUB1B abrogated cellular proliferation and induced drug sensitivity [4]. In gastric cancer, BUB1B knockdown hampered DNA repair and increased death in cisplatin-resistant cells, suggesting its role in promoting cisplatin resistance via Rad51-mediated DNA damage repair [5].

In conclusion, BUB1b is essential for proper cell division and its dysregulation contributes significantly to cancer progression. Studies using loss-of-function models across various cancers, such as lung adenocarcinoma, extrahepatic cholangiocarcinoma, multiple myeloma, and gastric cancer, have highlighted its oncogenic potential and its role in chemotherapy resistance. These findings suggest BUB1b could be a potential therapeutic target in these cancer types.