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CD28 delivers a unique signal leading to the selective recruitment of RelA and p52 NF-kappaB subunits on IL-8 and Bcl-xL gene promoters
- Source :
- Proceedings of the National Academy of Sciences of the United States of America. 101(16)
- Publication Year :
- 2004
-
Abstract
- CD28 is one of the most important costimulatory receptors necessary for full T lymphocyte activation. The CD28 receptor can enhance T cell antigen receptor (TCR) signals, as well as deliver independent signals. Indeed, CD28 engagement by B7 can generate TCR-independent signals leading to IκB kinase and NF-κB activation. Here we demonstrate that the TCR-independent CD28 signal leads to the selective transcription of survival (Bcl-xL) and inflammatory (IL-8andB cell activation factor, but not proliferative (IL-2), genes, in a NF-κB-dependent manner. CD28-stimulated T cells actively secrete IL-8, and Bcl-xL up-regulation protects T cells from radiation-induced apoptosis. The transcription of CD28-induced genes is mediated by the specific recruitment of RelA and p52 NF-κB subunits to target promoters. In contrast, p50 and c-Rel, which preferentially bind NF-κB sites on theIL-2gene promoter after anti-CD3 stimulation, are not involved. Thus, we identify CD28 as a key regulator of genes important for both survival and inflammation.
- Subjects :
- Transcription, Genetic
t-cell-activation
ikk-alpha
kinase complex
c-rel
bcl-x(l) expression
tcr engagement
cutting edge
in-vivo
costimulation
receptor
protein p50
transcription factor Rel
IκB kinase
protein p52
protein binding
gene targeting
chemistry.chemical_compound
T lymphocyte
bcl xl gene
Receptor
Promoter Regions, Genetic
Settore MED/35 - Malattie Cutanee e Veneree
Multidisciplinary
apoptosis
article
NF-kappa B
CD28
hemic and immune systems
Biological Sciences
cell secretion
CD28 antigen
immunoglobulin enhancer binding protein
protein subunit
T lymphocyte receptor
transcription factor RelA
b lymphocyte activation factor gene
binding site
cell protection
controlled study
gene
genetic regulation
genetic transcription
human
human cell
interleukin 2 gene
interleukin 8 gene
lymphocyte activation
priority journal
promoter region
radiation
signal transduction
upregulation
Antigens, CD28
Base Sequence
bcl-X Protein
Biological Transport
Cell Nucleus
DNA Primers
Gene Expression Regulation
Humans
Interleukin-8
Promoter Regions (Genetics)
Proto-Oncogene Proteins c-bcl-2
Signal Transduction
Transcription Factor RelA
Signal transduction
Transcription
chemical and pharmacologic phenomena
Biology
Promoter Regions
Genetic
CD28 Antigens
Antigens
T-cell receptor
NF-κB
Promoter
chemistry
Cancer research
Subjects
Details
- ISSN :
- 00278424
- Volume :
- 101
- Issue :
- 16
- Database :
- OpenAIRE
- Journal :
- Proceedings of the National Academy of Sciences of the United States of America
- Accession number :
- edsair.doi.dedup.....0b54dc5a79def0df07c1dc6ccb0674ba