Deubiquitylase UCHL3 regulates bi‐orientation and segregation of chromosomes during mitosis - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue FASEB Journal Année : 2020

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

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

Résumé

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
Origine : Publication financée par une institution

Dates et versions

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

Identifiants

Citer

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⟩
67 Consultations
130 Téléchargements

Altmetric

Partager

Gmail Facebook X LinkedIn More