PMID- 9831247
OWN - NLM
STAT- MEDLINE
DCOM- 19990202
LR  - 20081121
IS  - 1044-9523 (Print)
IS  - 1044-9523 (Linking)
VI  - 9
IP  - 11
DP  - 1998 Nov
TI  - Cooperative binding and synergistic activation by RelA and C/EBPbeta on the 
      intercellular adhesion molecule-1 promoter.
PG  - 949-59
AB  - Intercellular adhesion molecule-1 (ICAM-1) is up-regulated on numerous cell types 
      in response to inflammatory cytokines. Tumor necrosis factor-alpha (TNF-alpha) 
      activates the ICAM-1 promoter through a variant nuclear factor-kappaB (NF-kappaB) 
      site at -187/-178 bp upstream of the transcription start site. In this 
      investigation, we provide biochemical and functional evidence that an adjacent 
      CCAAT/enhancer binding protein (C/EBP) site and this variant NF-kappaB site 
      define a composite element for activation of the ICAM-1 promoter in certain cell 
      lines. We detected an endogenous TNF-alpha-inducible DNA-protein complex in 
      nuclear extracts from A549, HeLa, and EVC304 cells that contained both RelA and 
      C/EBPbeta but not other family members. Complex formation required intact C/EBP 
      and NF-kappaB sites and was absolutely dependent on translocation of RelA into 
      the nucleus. Complex formation and cooperative binding were also demonstrated 
      using recombinant proteins, and as above, both binding sites were necessary. 
      Interestingly, the RelA/C/EBPbeta complex was not detected in either Jurkat or 
      Raji cells, indicating cell type specificity. Functional studies with various 
      reporter gene constructs revealed that both binding sites were required for 
      maximal activation of the ICAM-1 promoter in response to TNF-alpha and for 
      synergistic activation by RelA and C/EBPbeta. This is the first detailed analysis 
      of how RelA and C/EBPbeta function to regulate ICAM-1 expression, and this study 
      has important implications for how this gene is activated in specific cell types.
FAU - Catron, K M
AU  - Catron KM
AD  - Department of Inflammatory Diseases, Boehringer Ingelheim Pharmaceuticals, Inc., 
      Ridgefield, Connecticut 06877-0368, USA. kcatron@bi-pharm.com
FAU - Brickwood, J R
AU  - Brickwood JR
FAU - Shang, C
AU  - Shang C
FAU - Li, Y
AU  - Li Y
FAU - Shannon, M F
AU  - Shannon MF
FAU - Parks, T P
AU  - Parks TP
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Cell Growth Differ
JT  - Cell growth & differentiation : the molecular biology journal of the American 
      Association for Cancer Research
JID - 9100024
RN  - 0 (CCAAT-Enhancer-Binding Proteins)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (NF-kappa B)
RN  - 0 (NF-kappa B p50 Subunit)
RN  - 0 (Nuclear Proteins)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (Proto-Oncogene Proteins c-rel)
RN  - 0 (Transcription Factor RelA)
RN  - 126547-89-5 (Intercellular Adhesion Molecule-1)
SB  - IM
MH  - Binding Sites
MH  - Biological Transport
MH  - CCAAT-Enhancer-Binding Proteins
MH  - Cell Nucleus/metabolism
MH  - DNA-Binding Proteins/genetics/*metabolism
MH  - Drug Synergism
MH  - HeLa Cells
MH  - Humans
MH  - Intercellular Adhesion Molecule-1/*genetics
MH  - NF-kappa B/genetics/*metabolism
MH  - NF-kappa B p50 Subunit
MH  - Nuclear Proteins/genetics/*metabolism
MH  - *Promoter Regions, Genetic
MH  - Proto-Oncogene Proteins/metabolism
MH  - Proto-Oncogene Proteins c-rel
MH  - Transcription Factor RelA
MH  - Transcriptional Activation
MH  - Tumor Cells, Cultured
EDAT- 1998/11/27 00:00
MHDA- 1998/11/27 00:01
CRDT- 1998/11/27 00:00
PHST- 1998/11/27 00:00 [pubmed]
PHST- 1998/11/27 00:01 [medline]
PHST- 1998/11/27 00:00 [entrez]
PST - ppublish
SO  - Cell Growth Differ. 1998 Nov;9(11):949-59.