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

Cancer Lett. 2020 Mar 31:473:98-106. doi: 10.1016/j.canlet.2019.12.042. Epub 2020 Jan 2.

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.

Keywords: Chromosomal stability; Kinesins; Mitosis; TRIM8.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aneuploidy
  • Animals
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism*
  • Cells, Cultured
  • Chromosomal Instability*
  • Embryo, Mammalian
  • Fibroblasts
  • HEK293 Cells
  • Humans
  • Kinesins / metabolism*
  • Mice
  • Micronuclei, Chromosome-Defective
  • Mitosis
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism*
  • Neural Stem Cells
  • Primary Cell Culture
  • Prometaphase / genetics
  • Protein Binding / genetics
  • Proteomics
  • Spindle Apparatus / metabolism*
  • Ubiquitin-Protein Ligases / metabolism*
  • beta Karyopherins / metabolism*

Substances

  • Carrier Proteins
  • Kifc1 protein, mouse
  • Nerve Tissue Proteins
  • TRIM8 protein, human
  • Trim8 protein, mouse
  • beta Karyopherins
  • Ubiquitin-Protein Ligases
  • Kif11 protein, mouse
  • Kinesins