PMID- 9545354
OWN - NLM
STAT- MEDLINE
DCOM- 19980521
LR  - 20210209
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 273
IP  - 16
DP  - 1998 Apr 17
TI  - Tumor necrosis factor-alpha- or lipopolysaccharide-induced expression of the 
      murine P-selectin gene in endothelial cells involves novel kappaB sites and a 
      variant activating transcription factor/cAMP response element.
PG  - 10068-77
AB  - Tumor necrosis factor-alpha (TNF-alpha) or lipopolysaccharide (LPS) increases 
      expression of the P-selectin gene in murine, but not in human, endothelial cells. 
      These mediators augment expression of a reporter gene driven by the murine, but 
      not the human, P-selectin promoter in transfected endothelial cells. The regions 
      from -593 to -474 and from -229 to -13 in the murine P-selectin promoter are 
      required for TNF-alpha or LPS to stimulate reporter gene expression. Within these 
      regions, we identified two tandem kappaB elements, a reverse-oriented kappaB site 
      and a variant activating transcription factor/cAMP response element (ATF/CRE), 
      that participate in TNF-alpha- or LPS-induced expression. The tandem kappaB 
      elements bound to NF-kappaB heterodimers and p65 homodimers, the reverse-oriented 
      kappaB site bound to p65 homodimers, and the variant ATF/CRE bound to nuclear 
      proteins that included activating transcription factor-2. Mutations in each 
      individual element eliminated binding to nuclear proteins and decreased by 20-60% 
      the TNF-alpha- or LPS-induced expression of a reporter gene driven by the murine 
      P-selectin promoter in transfected endothelial cells. Simultaneous mutations of 
      all elements further decreased, but did not abolish, induced expression. 
      Co-overexpression of p50 and p65 enhanced murine P-selectin promoter activity in 
      a kappaB site-dependent manner. These data indicate that the kappaB sites and the 
      variant ATF/CRE are required for TNF-alpha or LPS to optimally induce expression 
      of the murine P-selectin gene. The presence of these elements in the murine, but 
      not the human, P-selectin gene may explain in part why TNF-alpha or LPS 
      stimulates transcription of P-selectin in a species-specific manner.
FAU - Pan, J
AU  - Pan J
AD  - Department of Medicine, Warren Medical Research Institute, University of Oklahoma 
      Health Sciences Center, Oklahoma City, Oklahoma 73104, USA.
FAU - Xia, L
AU  - Xia L
FAU - Yao, L
AU  - Yao L
FAU - McEver, R P
AU  - McEver RP
LA  - eng
PT  - Journal Article
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Cyclic AMP Response Element-Binding Protein)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (NF-kappa B)
RN  - 0 (Nuclear Proteins)
RN  - 0 (P-Selectin)
RN  - 0 (Recombinant Fusion Proteins)
RN  - 0 (Transcription Factors)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - EC 1.13.12.- (Luciferases)
SB  - IM
MH  - Animals
MH  - Base Sequence
MH  - Binding Sites
MH  - CHO Cells
MH  - Cattle
MH  - Cells, Cultured
MH  - Consensus Sequence
MH  - Cricetinae
MH  - Cyclic AMP Response Element-Binding Protein/*metabolism
MH  - Endothelium, Vascular/drug effects/*metabolism
MH  - Gene Expression Regulation/*drug effects
MH  - Genes, Reporter
MH  - *Genetic Variation
MH  - Humans
MH  - Lipopolysaccharides/*pharmacology
MH  - Luciferases/biosynthesis
MH  - Mice
MH  - Molecular Sequence Data
MH  - NF-kappa B/*metabolism
MH  - Nuclear Proteins/metabolism
MH  - P-Selectin/*biosynthesis/genetics
MH  - Recombinant Fusion Proteins/biosynthesis
MH  - *Regulatory Sequences, Nucleic Acid
MH  - Sequence Alignment
MH  - Sequence Homology, Nucleic Acid
MH  - Species Specificity
MH  - Transcription Factors/*metabolism
MH  - Transfection
MH  - Tumor Necrosis Factor-alpha/*pharmacology
EDAT- 1998/05/23 00:00
MHDA- 1998/05/23 00:01
CRDT- 1998/05/23 00:00
PHST- 1998/05/23 00:00 [pubmed]
PHST- 1998/05/23 00:01 [medline]
PHST- 1998/05/23 00:00 [entrez]
AID - S0021-9258(18)46237-0 [pii]
AID - 10.1074/jbc.273.16.10068 [doi]
PST - ppublish
SO  - J Biol Chem. 1998 Apr 17;273(16):10068-77. doi: 10.1074/jbc.273.16.10068.