TRIM8 interacts with KIF11 and KIFC1 and controls bipolar spindle formation and chromosomal stability

Santina Venuto, Laura Monteonofrio, Flora Cozzolino, Maria Monti, Irene Appolloni, Tommaso Mazza, Diana Canetti, Vincenzo Giambra, Patrizio Panelli, Carmela Fusco, Gabriella Maria Squeo, Anna Irma Croce, Pietro Pucci, Paolo Malatesta, Silvia Soddu, Giuseppe Merla, Lucia Micale

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)98-106
Number of pages9
JournalCancer Letters
Volume473
DOIs
Publication statusPublished - Mar 31 2020

Keywords

  • Chromosomal stability
  • Kinesins
  • Mitosis
  • TRIM8

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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