Rel-dependent induction of A1 transcription is required to protect B cells from antigen receptor ligation-induced apoptosis.
In response to different extracellular signals, Rel/NF-kappaB transcription factors are critical regulators of apoptosis in a variety of cell types. Here we show that in normal B and T cells, expression of the Bcl-2 prosurvival homolog, A1, is rapidly induced in a Rel-dependent manner by mitogens. In B-cell lines derived from c-rel-/- mice, which like primary cells lacking Rel undergo apoptosis in response to antigen receptor ligation, constitutive expression of an A1 transgene inhibits this pathway to cell death. These findings are the first to show that Rel/NF-kappaB regulates physiologically the expression of a Bcl-2-like protein that is critical for the control of cell survival during lymphocyte activation.
The Walter and Eliza Hall Institute of Medical Research, Post Office, The Royal Melbourne Hospital, Parkville, Victoria 3050 Australia.
R J
RJ
Grumont
I J
IJ
Rourke
S
S
Gerondakis
D000818:Animals; D017209:Apoptosis / Q000235:genetics*; D001402:B-Lymphocytes / Q000378:metabolism*; D001483:Base Sequence; D004268:DNA-Binding Proteins / Q000235:genetics; D005786:Gene Expression Regulation / Q000235:genetics; D008213:Lymphocyte Activation / Q000187:drug effects; D051379:Mice; D018345:Mice, Knockout; D015778:Minor Histocompatibility Antigens; D008934:Mitogens / Q000494:pharmacology; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000235:genetics; D011401:Promoter Regions, Genetic / Q000235:genetics; D011506:Proteins / Q000235:genetics*; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2; D020569:Proto-Oncogene Proteins c-rel; D012333:RNA, Messenger / Q000378:metabolism; D011947:Receptors, Antigen, B-Cell / Q000378:metabolism*; D017422:Sequence Analysis, DNA; D013601:T-Lymphocytes / Q000378:metabolism; D014158:Transcription, Genetic / Q000235:genetics*
C096816:BCL2-related protein A1; D004268:DNA-Binding Proteins; D015778:Minor Histocompatibility Antigens; D008934:Mitogens; D016328:NF-kappa B; D011506:Proteins; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D020569:Proto-Oncogene Proteins c-rel; D012333:RNA, Messenger; D011947:Receptors, Antigen, B-Cell