Functional cooperation of the proapoptotic Bcl2 family proteins Bmf and Bim in vivo.
Bcl2-modifying factor (Bmf) is a member of the BH3-only group of proapoptotic proteins. To test the role of Bmf in vivo, we constructed mice with a series of mutated Bmf alleles that disrupt Bmf expression, prevent Bmf phosphorylation by the c-Jun NH(2)-terminal kinase (JNK) on Ser(74), or mimic Bmf phosphorylation on Ser(74). We report that the loss of Bmf causes defects in uterovaginal development, including an imperforate vagina and hydrometrocolpos. We also show that the phosphorylation of Bmf on Ser(74) can contribute to a moderate increase in levels of Bmf activity. Studies of compound mutants with the related gene Bim demonstrated that Bim and Bmf exhibit partially redundant functions in vivo. Thus, developmental ablation of interdigital webbing on mouse paws and normal lymphocyte homeostasis require the cooperative activity of Bim and Bmf.
Howard Hughes Medical Institute and Program in Molecular Medicine, University of Massachusetts Medical School, 373 Plantation Street, Worcester, MA 01605, USA.
Anette
A
Hübner
Julie
J
Cavanagh-Kyros
Mercedes
M
Rincon
Richard A
RA
Flavell
Roger J
RJ
Davis
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000502:physiology*; D000818:Animals; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000502:physiology*; D000072224:Bcl-2-Like Protein 11; D002470:Cell Survival; D005260:Female; D006706:Homeostasis; D052202:Hydrocolpos / Q000196:embryology; D048031:JNK Mitogen-Activated Protein Kinases / Q000502:physiology; D017880:Limb Deformities, Congenital / Q000196:embryology; D008214:Lymphocytes / Q000166:cytology / Q000502:physiology; D008565:Membrane Proteins / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008817:Mice, Mutant Strains; D009154:Mutation; D010766:Phosphorylation; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000502:physiology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000502:physiology*; D012694:Serine / Q000378:metabolism; D014621:Vagina / Q000002:abnormalities / Q000196:embryology
D048868:Adaptor Proteins, Signal Transducing; D051017:Apoptosis Regulatory Proteins; D000072224:Bcl-2-Like Protein 11; C000606776:Bcl2l11 protein, mouse; C435486:Bmf protein, mouse; D008565:Membrane Proteins; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D012694:Serine; D048031:JNK Mitogen-Activated Protein Kinases