Deubiquitylase UCHL3 regulates bi‐orientation and segregation of chromosomes during mitosis - Archive ouverte HAL Access content directly
Journal Articles FASEB Journal Year : 2020

Deubiquitylase UCHL3 regulates bi‐orientation and segregation of chromosomes during mitosis

Yongrong Liao
  • Function : Author
Charlotte Kleiss
  • Function : Author
Sadek Fournane
  • Function : Author
Matej Durik
  • Function : Author
Arantxa Agote‐arán
  • Function : Author
Laurent Brino
  • Function : Author
Radislav Sedlacek

Abstract

Equal segregation of chromosomes during mitosis ensures euploidy of daughter cells. Defects in this process may result in an imbalance in the chromosomal composition and cellular transformation. Proteolytic and non‐proteolytic ubiquitylation pathways ensure directionality and fidelity of mitotic progression but specific mitotic functions of deubiquitylating enzymes (DUBs) remain less studied. Here we describe the role of the DUB ubiquitin carboxyl‐terminal hydrolase isozyme L3 (UCHL3) in the regulation of chromosome bi‐orientation and segregation during mitosis. Downregulation or inhibition of UCHL3 leads to chromosome alignment defects during metaphase. Frequent segregation errors during anaphase are also observed upon inactivation of UCHL3. Mechanistically, UCHL3 interacts with and deubiquitylates Aurora B, the catalytic subunit of chromosome passenger complex (CPC), known to be critically involved in the regulation of chromosome alignment and segregation. UCHL3 does not regulate protein levels of Aurora B or the binding of Aurora B to other CPC subunits. Instead, UCHL3 promotes localization of Aurora B to kinetochores, suggesting its role in the error correction mechanism monitoring bi‐orientation of chromosomes during metaphase. Thus, UCHL3 contributes to the regulation of faithful genome segregation and maintenance of euploidy in human cells.
Fichier principal
Vignette du fichier
fj.202000769R.pdf (2.58 Mo) Télécharger le fichier
Origin : Publication funded by an institution

Dates and versions

hal-03097592 , version 1 (05-01-2021)

Identifiers

Cite

Katerina Jerabkova, Yongrong Liao, Charlotte Kleiss, Sadek Fournane, Matej Durik, et al.. Deubiquitylase UCHL3 regulates bi‐orientation and segregation of chromosomes during mitosis. FASEB Journal, 2020, 34 (9), pp.12751 - 12767. ⟨10.1096/fj.202000769r⟩. ⟨hal-03097592⟩
55 View
47 Download

Altmetric

Share

Gmail Facebook Twitter LinkedIn More