A paper in eLife brings hope for making use of the BubR1 protein in cancer treatment. Human cells contain 46 chromosomes, which are composed of DNA and other molecules. In cell division cycle, the chromosomes are duplicated and shared equally between the daughter cells. If this goes awry, the daughter cells have an incorrect number of chromosomes--a phenomenon called aneuploidy. As a result, cancer may develop. Cells use different methods to prevent aneuploidy, one of which is called spindle assembly checkpoint (SAC). The BubR1 protein is one important part of SAC, and it is essential for chromosomes to be equally divided into each daughter cell. Previous animal experiments demonstrate that low BubR1 levels contribute to aneuploidy as well as tumor, while overexpressing the protein can prevent these. But the question is that how BubR1 overexpression does these remains unclear. BubR1 has several known functional domains that together ensure mitotic fidelity and genome stability. Mayo Clinic investigators conducted this study to determine the role of each domain of the BubR1 molecule in suppressing cancer. Using Bub1b mutant transgenic mice, they found that BubR1N was necessary but not enough to suppress aneuploidy and tumor. Further, BubR1 lacking the internal Cdc20-binding domain was able to protect against both. Experiments in mouse cells indicated that high levels of the entire BubR1 protein and the mutant protein missing the middle region could prevent aneuploidy in several ways. Both systems had stronger SAC signaling, which could help to segregate the chromosomes properly. Further research will explore if BubR1 has the same effect in people, and if it’s possible to over-produce this protein to suppress tumors. “If you know how BubR1 does that, you can exploit it for therapeutic purposes,” said Dr. Jan van Deursen, a researcher at Mayo Clinic. Related protein of CusAb: Recombinant TLR2
