Journal
CANCER LETTERS
Volume 473, Issue -, Pages 98-106Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.canlet.2019.12.042
Keywords
TRIM8; Mitosis; Kinesins; Chromosomal stability
Categories
Funding
- Associazione Italiana per la Ricerca sul Cancro (AIRC) [14078, 18517]
- Italian Ministry of Health
- Italian Ministry of Health [GR-2011-02349694]
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The faithful inheritance of chromosomes is essential for the propagation of organisms. In eukaryotes, central to this process is the mitotic spindle. Recently, we have identified TRIM8 as a gene aberrantly expressed in gliomas whose expression reduces the clonogenic potential in the patients' glioma cells. TRIM8 encodes an E3 ubiquitin ligase involved in various pathological processes, including hypertrophy, antiviral defense, encephalopathy, and cancer development. To gain insights into the TRIM8 functions, we characterized the TRIM8 interactome in primary mouse embryonic neural stem cells using proteomics. We found that TRIM8 interacts with KIFC1, and KIF11/Eg5, two master regulators of mitotic spindle assembly and cytoskeleton reorganization. By exploring the TRIM8 role in the mitotic spindle machinery, we showed that TRIM8 localizes at the mitotic spindle during mitosis and plays a role in centrosome separation at the beginning of mitosis with a subsequent delay of the mitotic progression and impact on chromosomal stability.
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