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CD40 is a member of the tumor necrosis factor receptor superfamily and is a key signaling molecule expressed by antigen-presenting cells of the immune system. In a previous paper, we demonstrated that the expression of CD40 is regulated by both post-transcriptional and post-translational processes. In this paper, we show that basal (constitutive) CD40 gene expression is regulated by a TATA-less promoter, with Sp1 as a key transcription factor. Two Sp1 binding regions were identified in the mouse CD40 promoter at positions -59 to -50 and -74 to -66. Surprisingly, Sp1-mediated CD40 transcription was reduced following lipopolysaccharide stimulation and was associated with a time-dependent reduction in Sp1 DNA binding activity. This reduction seemed to be mediated by phosphorylation of the Sp1 molecule. We also show here that CD40 expression in lipopolysaccharide-stimulated cells is up-regulated by NF-kappaB through two distinct sites. One of these sites (-128 to -119) was shown to bind p50 and p65 members of the NF-kappaB family, while the other site (-562 to -553) bound only p65. Transfectants of p65 were generated using RAW 264 cells, and it was shown that the up-regulation of CD40 mRNA expression was dependent on the presence of the p65 molecule.

Original publication

DOI

10.1074/jbc.M109889200

Type

Journal article

Journal

J Biol Chem

Publication Date

15/03/2002

Volume

277

Pages

8890 - 8897

Keywords

Antigens, CD40, Base Sequence, DNA, DNA-Binding Proteins, Gene Expression Regulation, Lipopolysaccharides, Molecular Sequence Data, NF-kappa B, Phosphorylation, RNA, Messenger, Sp1 Transcription Factor, Sp3 Transcription Factor, Transcription Factors, Transcription, Genetic