Fiche publication
Date publication
octobre 2014
Journal
Oncogene
Auteurs
Membres identifiés du Cancéropôle Est :
Dr CHARVET Céline
Tous les auteurs :
Lindner SE, Wissler M, Gründer A, Aumann K, Ottina E, Peintner L, Brauns-Schubert P, Preiss F, Herzog S, Borner C, Charvet C, Villunger A, Pahl HL, Maurer U
Lien Pubmed
Résumé
The antiapoptotic BCL-2 protein MCL-1, which opposes mitochondrial outer membrane permeabilization, was shown to have a crucial role in the survival of hematopoietic cells. We have previously shown that, upon loss of phosphatidylinositol 3-kinase signaling, S159 of MCL-1 is phosphorylated by glycogen synthase kinase-3 (GSK-3), earmarking MCL-1 for enhanced ubiquitylation and degradation. In this study, we introduced MCL-1(wt) or the phosphorylation-deficient mutant MCL-1(S159A) in mouse BM cells, followed by adoptive transfer to recipient mice. Mice expressing MCL-1(S159A) exhibited significantly elevated white blood cell and lymphocyte counts, whereas no effect was observed on the distribution of T and B lymphocyte subsets or the numbers of monocytes, red blood cells or platelets. Expression of MCL-1(S159A) in Eμ-Myc transgenic bone marrow significantly accelerated the onset of disease, and these mice displayed increased spleen weights compared with Eμ-Myc/MCL-1(wt) mice. Our data demonstrate that the absence of MCL-1 S159 phosphorylation provides a survival advantage for hematopoietic cells in vivo and facilitates oncogenesis.
Mots clés
Animals, Bone Marrow Transplantation, Cell Survival, Green Fluorescent Proteins, genetics, Humans, Leukocytes, metabolism, Lymph Nodes, cytology, Lymphoma, metabolism, Mice, Inbred C57BL, Mice, Transgenic, Mutation, Myeloid Cell Leukemia Sequence 1 Protein, genetics, Phosphorylation, Spleen, cytology
Référence
Oncogene. 2014 Oct 30;33(44):5221-4
