GSK3-SCF(FBXW7) targets JunB for degradation in G2 to preserve chromatid cohesion before anaphase - CNRS - Centre national de la recherche scientifique Accéder directement au contenu
Article Dans Une Revue Oncogene Année : 2012

GSK3-SCF(FBXW7) targets JunB for degradation in G2 to preserve chromatid cohesion before anaphase

B. Perez-Benavente
  • Fonction : Auteur
J. L. Garcia
  • Fonction : Auteur
M. S. Rodriguez
  • Fonction : Auteur
A. Pineda-Lucena
  • Fonction : Auteur
J. Font De Mora
  • Fonction : Auteur
R. Farras
  • Fonction : Auteur

Résumé

JunB, an activator protein-1 (AP-1) transcription factor component, acts either as a tumor suppressor or as an oncogene depending on the cell context. In particular, JunB is strongly upregulated in anaplastic lymphoma kinase (ALK)-positive anaplastic large cell lymphoma (ALCL) where it enhances cell proliferation. Although its overexpression is linked to lymphomagenesis, the mechanisms whereby JunB promotes neoplastic growth are still largely obscure. Here, we show that JunB undergoes coordinated phosphorylation-dependent ubiquitylation during the G2 phase of the cell cycle. We characterized a critical consensus phospho-degron that controls JunB turnover and identified GSK3 and SCF(FBXW7) as, respectively, the kinase and the E3 ubiquitin ligase responsible for its degradation in G2. Pharmacological or genetic inactivation of the GSK3-FBXW7-JunB axis induced accumulation of JunB in G2/M and entailed transcriptional repression of the DNA helicase DDX11, leading to premature sister chromatid separation. This abnormal phenotype due to dysregulation of the GSK3beta/JunB/DDX11 pathway is phenocopied in ALK-positive ALCL. Thus, our results reveal a novel mechanism by which mitosis progression and chromatid cohesion are regulated through GSK3/SCF(FBXW7)-mediated proteolysis of JunB, and suggest that JunB proteolysis in G2 is an essential step in maintaining genetic fidelity during mitosis.Oncogene advance online publication, 18 June 2012; doi:10.1038/onc.2012.235.

Dates et versions

hal-02193072 , version 1 (24-07-2019)

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Citer

B. Perez-Benavente, J. L. Garcia, M. S. Rodriguez, A. Pineda-Lucena, Marc Piechaczyk, et al.. GSK3-SCF(FBXW7) targets JunB for degradation in G2 to preserve chromatid cohesion before anaphase. Oncogene, 2012, 1 (1), pp.1--11. ⟨10.1038/onc.2012.235⟩. ⟨hal-02193072⟩
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