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Article Dans Une Revue Oncogene Année : 2018

The oncogenic tyrosine kinase Lyn impairs the pro-apoptotic function of Bim.

Lazaro E Aira
  • Fonction : Auteur
Elodie Villa
  • Fonction : Auteur
Pascal Colosetti
Parvati Gamas
  • Fonction : Auteur
Laurie Signetti
  • Fonction : Auteur
Sandrine Obba
  • Fonction : Auteur
Emma Proics
  • Fonction : Auteur
Beatrice Bailly-Maitre
  • Fonction : Auteur
Arnaud Jacquel
Guillaume Robert
  • Fonction : Auteur
Frédéric Luciano
Jean-Ehrland Ricci
  • Fonction : Auteur
Patrick Auberger
  • Fonction : Auteur
Sandrine Marchetti
  • Fonction : Auteur

Résumé

Phosphorylation of Ser/Thr residues is a well-established modulating mechanism of the pro-apoptotic function of the BH3-only protein Bim. However, nothing is known about the putative tyrosine of this Bcl-2 family member and its potential impact on Bim function and subsequent Bax/Bak-mediated cytochrome c release and apoptosis. As we have previously shown that the tyrosine kinase Lyn could behave as an anti-apoptic molecule, we investigated whether this Src family member could directly regulate the pro-apoptotic function of Bim. In the present study, we show that Bim is phosphorylated onto tyrosine residues 92 and 161 by Lin, which results is an inhibition of its pro-apoptotic function. Mechanistically, we show that Lyn-dependent tyrosine phosphorylation of Bim increases its interaction with anti-apoptic members such as Bcl-xL, therefore limiting mitochondrial outer membrane permeabilization and subsequent apoptosis. Collectively, our data uncover one molecular mechanism through which the oncogenic tyrosine kinase Lyn negatively regulates the mitochondrial apoptic pathway, which may contribute to the transformation and/or the chemotherapeutic resistance of cancer cells.

Domaines

Cancer
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Dates et versions

inserm-01814383 , version 1 (13-06-2018)

Identifiants

Citer

Lazaro E Aira, Elodie Villa, Pascal Colosetti, Parvati Gamas, Laurie Signetti, et al.. The oncogenic tyrosine kinase Lyn impairs the pro-apoptotic function of Bim.. Oncogene, 2018, 37 (16), pp.2122 - 2136. ⟨10.1038/s41388-017-0112-0⟩. ⟨inserm-01814383⟩
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