Proapoptotic BH3-only Bcl-2 family member Bik/Blk/Nbk is expressed in hemopoietic and endothelial cells but is redundant for their programmed death.
The BH3-only members of the Bcl-2 protein family are essential for initiation of programmed cell death and stress-induced apoptosis. We have determined the expression pattern in mice of the BH3-only protein Bik, also called Blk or Nbk, and examined its physiological function by gene targeting. We found that Bik is expressed widely in the hematopoietic compartment and in endothelial cells of the venous but not arterial lineages. Nevertheless, its loss did not increase the numbers of such cells in mice or protect hematopoietic cells in vitro from apoptosis induced by cytokine withdrawal or diverse other cytotoxic stimuli. Moreover, whereas loss of the BH3-only protein Bim rescued mice lacking the prosurvival protein Bcl-2 from fatal polycystic kidney disease and lymphopenia, loss of Bik did not. These results indicate that any function of Bik in programmed cell death and stress-induced apoptosis must overlap that of other BH3-only proteins.
Coultas
Leigh
L
The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3050, Australia.
Bouillet
Philippe
P
Stanley
Edouard G
EG
Brodnicki
Thomas C
TC
Adams
Jerry M
JM
Strasser
Andreas
A
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D042783:Endothelial Cells / Q000166:cytology / Q000378:metabolism*; D005260:Female; D017353:Gene Deletion; D020869:Gene Expression Profiling; D017930:Genes, Reporter / Q000235:genetics; D006410:Hematopoiesis; D006413:Hematopoietic System / Q000002:abnormalities / Q000166:cytology / Q000378:metabolism*; D007668:Kidney / Q000002:abnormalities; D051379:Mice; D018345:Mice, Knockout; D024101:Mitochondrial Proteins; D018919:Neovascularization, Physiologic; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism
D048868:Adaptor Proteins, Signal Transducing; D051017:Apoptosis Regulatory Proteins; C111741:Bik protein, mouse; D002352:Carrier Proteins; D024101:Mitochondrial Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger