TRIM8 interacts with KIF11 and KIFC1 and controls bipolar spindle formation and chromosomal stability. (31st March 2020)

• Record Type: Journal Article
• Authors: Venuto, Santina; Monteonofrio, Laura; Cozzolino, Flora; Monti, Maria; Appolloni, Irene; Mazza, Tommaso; Canetti, Diana; Giambra, Vincenzo; Panelli, Patrizio; Fusco, Carmela; Squeo, Gabriella Maria; Croce, Anna Irma; Pucci, Pietro; Malatesta, Paolo; Soddu, Silvia; Merla, Giuseppe; Micale, Lucia
• Is Part Of: Cancer letters. Volume 473(2020)
• Page Start: 98
• Page End: 106
• Publication Date: 2020-03-31
• Subjects: TRIM8 -- Mitosis -- Kinesins -- Chromosomal stability; Cancer -- Periodicals; Neoplasms -- Periodicals; Cancer -- Périodiques; Electronic journals; 616.994
• DOI: 10.1016/j.canlet.2019.12.042
• Languages: English
• ISSNs: 0304-3835

Abstract

Abstract: 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. Highlights: The TRIM8 interactome in neural stem cells was characterized using proteomic. TRIM8 interacts with two master regulators of mitotic spindle assembly. TRIM8 localizes at the mitotic spindle during mitosis. TRIM8 plays a role in centrosome separation at the beginning of mitosis. TRIM8 silencing delays the mitotic progression and impacts chromosomal stability.