A T-CELL ENHANCER COOPERATES WITH NF-KAPPA-B TO YIELD CYTOKINE INDUCTION OF E-SELECTIN GENE-TRANSCRIPTION IN ENDOTHELIAL-CELLS

作者：VANHUIJSDUIJNEN RH^*; WHELAN J; PESCINI R; BECKERANDRE M; SCHENK AM; DELAMARTER JF

来源：Journal of Biological Chemistry, 1992, 267(31): 22385-22391.

ELAM1 (endothelial leukocyte adhesion molecule 1, also known as E-selectin) is a highly tissue-specific adhesion molecule that is transiently and exclusively expressed on cytokine-induced endothelial cells. We have identified two proximal ELAM1 promoter elements and their DNA-binding factors that are, in addition to NF-kappaB, essential for ELAM1 transcription. Mutation of either element in promoter constructs carrying the first 383 nucleotides of the ELAM1 promoter markedly diminished the expression of a fused chloramphenicol acetyltransferase reporter gene. Although multimers of either element failed to display enhancer activity on its own, fusion of the most upstream of these to the NF-kappaB element had a strong stimulatory effect. This site, ACATCAT, is recognized by a factor we have called NF-ELAM1. The site corresponds to NF-ELAM1's preferential binding sequence (A/T)CA(G/T)CA(G/T) as determined in a target definition assay. This element is identical to the T-cell deltaA enhancer found in the T-cell receptor-alpha, -beta, and CD3delta genes. Our results suggest that the deltaA/NF-ELAM1 element can function as a modulator of NF-kappaB in endothelial cells both as well as a T-cell enhancer.

• 出版日期1992-11-5