How a "Mob Breaker" Protein Ensures Accurate Cell Division

In 2000, researchers discovered that mutations that inactivate a gene known as TRIM37 causes a developmental disease called Mulibrey nanism. The extremely rare inherited disorder leads to growth delays and abnormalities in several organs, causing afflictions of the heart, muscles, liver, brain and eyes. In addition, Mulibrey nanism patients exhibit high rates of cancer and are infertile.

In 2016, UC San Diego School of Biological Sciences researchers in the labs of Professors Karen Oegema and Arshad Desai began understanding how TRIM37, when operating normally, plays a key role in preventing conditions that lead to Mulibrey nanism. They linked TRIM37 to spindles, which separate chromosomes during cell division, and centrosomes, the spherical organizing structures at each end of spindles.

TRIM37, the researchers found, is critical in preventing extra spindle poles from forming, which obstructs normal cell division, generating daughter cells with incorrect chromosomal content. But how does TRIM37 prevent the formation of extra spindle poles?

Recently published research describes how TRIM37 prevents the formation of abnormal assemblies of centrosomal proteins that can become extra spindle poles. Desai describes TRIM37 as a type of “mob breaker” that recognizes abnormal clusters of centrosomal proteins and degrades them to prevent them from forming extra spindle poles that create problems for chromosome segregation. In this manner, TRIM37 ensures accurate genome transmission during cell division.

“As loss of TRIM37 is associated with Mulibrey nanism, a tumor-prone human genetic disorder, the work also provides an explanation for what is happening at the cellular level to cause this disease,” said Desai.

Interestingly, the way TRIM37 works to prevent formation of extra spindle poles is similar to how viruses such as HIV are detected and eliminated by related TRIM proteins once they get inside cells. These findings highlight a similar molecular logic by which cells ensure accurate cell division and fight viral infections.

Reference: Bellaart A, Brambila A, Xu J, et al. TRIM37 prevents ectopic spindle pole assembly by peptide motif recognition and substrate-dependent oligomerization. Nat Struct Mol Biol. 2025. doi:10.1038/s41594-025-01562-0