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PMID: 8698809 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Bcl-2 down-regulates the activity of transcription factor NF-kappaB induced upon apoptosis.

The Journal of cell biology ·Vol. 134 ·No. 1 ·1996-07-00 ·Pages 13-23

Grimm S, Bauer MK, Baeuerle PA, Schulze-Osthoff K

Abstract

Among the many target genes of the transcription factor NF-kappaB are p53 and c-myc, both of which are involved in apoptosis. This prompted us to investigate the role of NF-kappaB in this process. We report that NF-kappaB is potently activated upon serum starvation, a condition leading to apoptosis in 293 cells. Similar to Bcl-2, a transdominant-negative mutant of the NF-kappaB p65 subunit partially inhibited apoptosis, indicating a direct involvement of the transcription factor in induction of cell death. As expected, the p65 mutant suppresses kappaB-dependent gene expression. Surprisingly, transiently or stably overexpressed Bcl-2 had the same effect. The transcription inhibitory activity of the two proteins correlated with their cell death protective potential. Like Bcl-2, the related protein Bcl-xL but not Bcl-xS was able to suppress kB-dependent transcription. Bcl-2 inhibited NF-kappaB activity by an unusual mechanism. It did not prevent the release of IkappaB in the cytoplasm but down-modulated the transactivating potential of nuclear p65. These data show that NF-kappaB can participate in apoptosis. We suggest that at least part of the anti-apoptotic potential of Bcl-2 may be explained from a hitherto undiscovered activity of Bcl-2 in controlling nuclear gene expression.

MeSH Terms
Animals Apoptosis Biological Transport Cell Line Cell Nucleus/metabolism Chlorocebus aethiops Culture Media DNA-Binding Proteins/metabolism Gene Expression Regulation Humans NF-kappa B/metabolism Proto-Oncogene Proteins/metabolism Proto-Oncogene Proteins c-bcl-2 Transcription, Genetic Transcriptional Activation
Chemicals
Culture Media DNA-Binding Proteins NF-kappa B Proto-Oncogene Proteins Proto-Oncogene Proteins c-bcl-2
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Grimm S
Institute of Biochemistry and Molecular Biology, Albert-Ludwigs-University, Freiburg, Germany.
Bauer M K
Baeuerle P A
Schulze-Osthoff K
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Article Info
Journal
The Journal of cell biology
Abbr.
J Cell Biol
ISSN
0021-9525
DOI
10.1083/jcb.134.1.13
Published
1996-07-00
Pages
13-23
Language
English
Region
United States
NLM ID
0375356
PMCID
PMC2120920
Subset
IM
External Links
PubMed source DOI: 10.1083/jcb.134.1.13 PMC Full Text View journal details
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