BUB1B

BUB1B, also known as BUB1 mitotic checkpoint serine/threonine kinase BUBR1, is a gene that encodes a serine/threonine kinase integral to the spindle assembly checkpoint. It is a member of the BUB1 family of checkpoint proteins and is conserved across eukaryotes.

BUB1B plays a central role in monitoring chromosome-kinetochore attachments during mitosis and in preventing the onset of anaphase until all chromosomes are properly attached to the spindle. It contributes to the signaling that inhibits the Anaphase-Promoting Complex/Cyclosome (APC/C) through the formation of the mitotic checkpoint complex (MCC), thereby delaying progression to anaphase if defects are detected.

In cells, BubR1 localizes to kinetochores during mitosis and forms the MCC together with BUB3, MAD2, and CDC20. Its kinase activity and interactions with these and other checkpoint components regulate the strength and duration of the checkpoint signal, coordinating timely and accurate chromosome segregation.

Pathogenic variants in BUB1B are associated with Mosaic Variegated Aneuploidy (MVA), a rare disorder characterized by mosaic chromosomal abnormalities and an elevated risk of cancer. Many pathogenic variants reduce BubR1 function, with haploinsufficiency described as a disease mechanism in some cases.

Beyond MVA, alterations in BUB1B have been observed in various sporadic cancers and are linked to chromosomal instability. Research continues into the gene’s role as a biomarker of genomic instability and as a potential target for therapeutic intervention in cancers driven by mitotic checkpoint defects.