UCSD - University of California - San Diego
09/02/2025 | Press release | Distributed by Public on 09/02/2025 12:37
Researchers Decipher Gene’s Critical Function That Prevents Disease
Published Date
September 02, 2025Article Content
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.
The image shows a normal mitotic cell (left) compared to a cell lacking TRIM37 (right), with spindle microtubules (green), centrosomal protein centrobin (magenta) and DNA (white). Normal cells have two spindle poles that ensure proper cell division. Cells lacking TRIM37 frequently have extra spindle poles, containing a cluster of centrobin molecules, that disrupt proper cell division. Patients with Mulibrey namism lack TRIM37 and their cells show similar extra spindle poles.
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.
Pathways in Biological Sciences graduate student Andrew Bellaart (right) and graduate student Jiawei Xu helped lead the newly published study.
The lead author of the study is Andrew Bellaart, a graduate student who was supported through Pathways in Biological Sciences (PiBS), an innovative National Institutes of Health-funded program designed to instill students with valuable scientific, leadership and communication skills. The program's leaders mentor PiBS students as they become immersed in different scientific fields, ethics and other areas. "Programs like PiBS are highly significant to the development of the next generation of independent and leading scientific minds," said Desai. A second graduate student, Jiawei Xu, also significantly contributed to the research and shares co-first authorship. The work also highlights the synergy derived from collaboration between experts in cell biology (Oegema and Desai) and structural biology (Corbett) in the School of Biological Sciences.
The research paper, "TRIM37 prevents ectopic spindle pole assembly by peptide motif recognition and substrate-dependent oligomerization," was published on May 25, 2025 in Nature Structural and Molecular Biology. The authors of the study were: Andrew Bellaart, Amanda Brambila, Jiawei Xu, Francisco Mendez Diaz, Amar Deep, John Anzola, Franz Meitinger, Midori Ohta, Kevin D. Corbett, Arshad Desai and Karen Oegema. The research was supported by the National Institutes of Health (R01 GM074207, R01 GM074215 and R35 GM144121); Institutional Research Career and Academic Development Awards; the National Institute of General Medical Sciences (K12 GM068524 and T32 GM133351); and the Ludwig Institute for Cancer Research.
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