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Differential inhibition of UVB‐induced AP‐1 and NF‐κB transactivation by components of the jun bZIP domain
Author(s) -
Cooper Simon,
RangerMoore James,
Bowden Tim G.
Publication year - 2005
Publication title -
molecular carcinogenesis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.254
H-Index - 97
eISSN - 1098-2744
pISSN - 0899-1987
DOI - 10.1002/mc.20101
Subject(s) - transactivation , bzip domain , biology , transcription factor , basic helix loop helix leucine zipper transcription factors , leucine zipper , activating transcription factor , atf3 , mutant , microbiology and biotechnology , immunoprecipitation , phosphorylation , transcription (linguistics) , nfkb1 , dna binding protein , cell culture , gene expression , promoter , biochemistry , gene , genetics , linguistics , philosophy
Potential targets for chemoprevention of nonmelanoma skin cancer include UV‐induced nuclear factor κB (NF‐κB) and activator protein‐1 (AP‐1) activation in keratinocytes. Inhibition of both these ultraviolet light B (UVB)‐induced transcription factors has been shown with the dominant‐negative c‐ jun mutant, TAM67; however, its mechanism of action has not yet been determined. Here we demonstrated that transient transfection of a mouse keratinocyte cell line (308) with a dominant‐negative phosphorylation mutant of c‐Jun before exposure to 250 J/m 2 UVB inhibits transactivation mediated by both AP‐1 and NF‐κB transcription factors to levels below those of UVB exposed controls. Through the utilization of immunoprecipitation techniques, protein‐protein interactions between NF‐κB family members IκBα, IκBβ, p50, and p65 (Rel‐A) were identified with an Xpress tagged dominant‐negative c‐Jun (TAM67) protein. Expression of the leucine zipper domain of the TAM67 protein inhibited UVB‐induced NF‐κB transactivation but not AP‐1 transactivation. Expression of the bZIP domain of the TAM67 protein was able to inhibit transactivation mediated by both transcription factors. These data demonstrate that TAM67 is able to inhibit two significant UVB‐induced molecular targets AP‐1 and NF‐κB, and that the inhibition of these two transcription factor families is potentially due to protein‐protein interactions between different regions of the dominant‐negative c‐Jun protein. © 2005 Wiley‐Liss, Inc.