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AP‐1 activity is negatively regulated by cannabinol through inhibition of its protein components, c‐fos and c‐jun
Author(s) -
Faubert Barbara L.,
Kaminski Norbert E.
Publication year - 2000
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1002/jlb.67.2.259
Subject(s) - biology , activator (genetics) , phosphorylation , mapk/erk pathway , microbiology and biotechnology , protein kinase a , kinase , signal transduction , ap 1 transcription factor , receptor , cannabinoid , biochemistry , transcription factor , gene
Abstract Regulation of the activator protein‐1 (AP‐1) complex is very intricate because it involves phosphorylation state, protein‐protein, and protein‐DNA interactions. In these studies, the regulation of AP‐1 activity, with emphasis on c‐fos and c‐jun regulation, was investigated using cannabinol (CBN) in primary mouse splenocytes in vitro. Cannabinoid compounds exhibit immunosuppressive actions that are putatively mediated through Gi‐protein coupled receptors that negatively regulate adenylate cyclase. However, recent studies suggest that cannabi‐noids modulate other signaling cascades. Indeed, we demonstrate that CBN inhibited binding to AP‐1‐containing sites from the interleukin‐2 promoter. This inhibition of binding was, in part, due to decreased nuclear expression of c‐fos and c‐jun. We further determined that the effects of CBN were due to posttranslational modifications of these phosphoproteins and showed that CBN inhibited the activation of ERK MAP kinases. Thus, cannabinoid‐induced immunosuppression involves disruption of the ERK signaling cascade. J. Leukoc. Biol. 67: 259–266; 2000.