Journal article
Alternative splicing of Bim and Erk-mediated Bim EL phosphorylation are dispensable for hematopoietic homeostasis in vivo
C Clybouw, D Merino, T Nebl, F Masson, M Robati, L O'Reilly, A Hübner, RJ Davis, A Strasser, P Bouillet
Cell Death and Differentiation | NATURE PUBLISHING GROUP | Published : 2012
DOI: 10.1038/cdd.2011.198
Abstract
The pro-apoptotic BH3-only protein Bim has a major role in hematopoietic homeostasis, particularly in the lymphocyte compartment, where it strongly affects immune function. The three major Bim isoforms (BimEL, BimL and BimS) are generated by alternative splicing. BimEL, the most abundant isoform, contains a unique sequence that has been reported to be the target of phosphorylation by several MAP kinases. In particular, Erk1/2 has been shown to interact with BimEL through the DEF2 domain of BimEL and specifically phosphorylate this isoform, thereby targeting it for ubiquitination and proteasomal degradation. To examine the physiological importance of this mechanism of regulation and of the al..
View full abstractGrants
Awarded by National Cancer Institute
Funding Acknowledgements
We are grateful to E Sutherland and G Siciliano for expert animal care; B Helbert and C Young for genotyping; J Corbin for automated blood analysis; Dr. JM Adams for insightful discussions. This work was supported by the Australian NHMRC (program grant 461221, Independent Research Institutes Infrastructure Support Scheme grant 361646 and Career Development Award), Cancer Council Victoria, the Leukemia and Lymphoma Society (Specialized Center of Research grant 7015), the French Association pour la Recherche contre le Cancer postdoctoral fellowship and INSERM/NHMRC exchange program (to C Clybouw), the Australian Research Council (to D Merino), the Viertel Charitable Foundation (to P Bouillet) and infrastructure support from the NHMRC (IRISS) and the Victorian State Government (OIS).