Rel/NF-kappaB represses bcl-2 transcription in pro-B lymphocytes.
The mechanisms controlling programmed cell death (PCD) during early B cell development are not well understood. Members of both the Bcl-2 family of apoptosis-related proteins and the nuclear factor-kappa B/Rel (NF-kappaB/Rel) family of transcription factors are expressed differentially during B cell development. To date, however, no direct interactions between these two families have been demonstrated. The FL5.12 cell line represents a model for progenitor B cell development. Such cells reproducibly undergo PCD upon IL-3 withdrawal. The signal to enter the apoptotic pathway is mediated by a shift in the ratio of Bcl-2:Bax. While bax levels remain constant, bcl-2 transcription rate, steady-state mRNA, and protein levels decrease. Analysis of the bcl-2 promoter reveals 3 kappaB sites functionally able to bind kappaB factors from FL5.12 nuclear extracts. Cotransfection studies demonstrate that NF-kappaB factors can repress bcl-2 transcription and that site-directed mutagenesis of the kappaB motifs abolishes this repression. These studies suggest that NF-kappaB mediates PCD in pro-B cells through transcriptional repression of the survival gene bcl-2, thus shifting the bcl-2:bax ratio in favor of death-promoting complexes.
Sohur
U S
US
Department of Microbiology & Immunology, Vanderbilt University School of Medicine, Nashville, TN 37232-2363, USA.
Dixit
M N
MN
Chen
C L
CL
Byrom
M W
MW
Kerr
L A
LA
D000818:Animals; D017209:Apoptosis / Q000235:genetics*; D001402:B-Lymphocytes / Q000473:pathology* / Q000502:physiology*; D001483:Base Sequence; D002460:Cell Line; D018507:Gene Expression Regulation, Developmental; D019254:Genes, bcl-2; D020573:Genes, rel; D051379:Mice; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D016328:NF-kappa B / Q000235:genetics*; D014158:Transcription, Genetic
D016328:NF-kappa B