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PMID: 15079071 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

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.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 101 ·No. 16 ·2004-04-20 ·Pages 6098-103

Marinari B, Costanzo A, Marzano V, Piccolella E, Tuosto L

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 IkappaB kinase and NF-kappaB activation. Here we demonstrate that the TCR-independent CD28 signal leads to the selective transcription of survival (Bcl-xL) and inflammatory (IL-8 and B cell activation factor, but not proliferative (IL-2), genes, in a NF-kappaB-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-kappaB subunits to target promoters. In contrast, p50 and c-Rel, which preferentially bind NF-kappaB sites on the IL-2 gene promoter after anti-CD3 stimulation, are not involved. Thus, we identify CD28 as a key regulator of genes important for both survival and inflammation.

MeSH Terms
Base Sequence Biological Transport CD28 Antigens/physiology Cell Nucleus/metabolism DNA Primers Gene Expression Regulation/physiology Humans Interleukin-8/genetics NF-kappa B/genetics,physiology Promoter Regions, Genetic Proto-Oncogene Proteins c-bcl-2/genetics Signal Transduction/physiology Transcription Factor RelA Transcription, Genetic bcl-X Protein
Chemicals
BCL2L1 protein, human CD28 Antigens DNA Primers Interleukin-8 NF-kappa B Proto-Oncogene Proteins c-bcl-2 Transcription Factor RelA bcl-X Protein
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Marinari Barbara
Department of Cellular and Developmental Biology, University of Rome La Sapienza, 00185 Rome, Italy.
Costanzo Antonio
Marzano Valeria
Piccolella Enza
Tuosto Loretta
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.0308688101
Published
2004-04-20
Epub
2004-00-12
Pages
6098-103
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC395929
Subset
IM
External Links
PubMed source DOI: 10.1073/pnas.0308688101 PMC Full Text View journal details
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