Journal article
TRIM17 and TRIM28 antagonistically regulate the ubiquitination and anti-apoptotic activity of BCL2A1
L Lionnard, P Duc, MS Brennan, AJ Kueh, M Pal, F Guardia, B Mojsa, MA Damiano, S Mora, I Lassot, R Ravichandran, C Cochet, A Aouacheria, PR Potts, MJ Herold, S Desagher, J Kucharczak
Cell Death and Differentiation | NATURE PUBLISHING GROUP | Published : 2019
Abstract
BCL2A1 is an anti-apoptotic member of the BCL-2 family that contributes to chemoresistance in a subset of tumors. BCL2A1 has a short half-life due to its constitutive processing by the ubiquitin–proteasome system. This constitutes a major tumor-suppressor mechanism regulating BCL2A1 function. However, the enzymes involved in the regulation of BCL2A1 protein stability are currently unknown. Here, we provide the first insight into the regulation of BCL2A1 ubiquitination. We present evidence that TRIM28 is an E3 ubiquitin-ligase for BCL2A1. Indeed, endogenous TRIM28 and BCL2A1 bind to each other at the mitochondria and TRIM28 knock-down decreases BCL2A1 ubiquitination. We also show that TRIM17 ..
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Awarded by Agence Nationale de la Recherche
Funding Acknowledgements
This work was supported by grants from La Ligue contre le Cancer, regional committees of Drome, Herault and Lozere (to J.K.) and Gard (to S.D.), the Centre National de la Recherche Scientifique (CNRS), Leukaemia Foundation Australia, and Cancer Council Victoria Venture Grant (to M.J.H.), World Cancer Research 15-0177 (to P.R.P.). L.L. was supported by the University of Montpellier, La Ligue Nationale contre le Cancer and by the Programme de mobilite scientifique from the embassy of France in Australia. J.K. was supported by the University of Lyon and was recipient of a delegation CNRS program. The authors thank the Protein Science Facility of the SFR Biosciences Lyon for their valuable expertize and technical assistance in mass spectrometry analysis and Aurelie CornutThibault for preparation of samples. The authors also thank the staff of Montpellier Genomic Collection platform for providing TRIM28 cDNA clones and the imaging facility MRI, member of the National Infrastructure France-BioImaging supported by the French National Research Agency (ANR-10-INBS-04, "Investments for the future") for Microscopy and Cytometry Analysis. The authors are grateful to Drs. Nathalie Bonnefoy, Veronique Baldin, Olivier Coux, Damien Gregoire, Florence Cammas, and Anne-Marie Marini for fruitful discussions and reagents, Gilles Salles (HCL, Lyon-Sud) for support during the early stages of this work, and John A. Hickman for critical reading of the manuscript.