Transcriptional and Posttranscriptional Regulation of cJun Expression

When cells are exposed to the tumor promoter phorbol-ester 12-o-tetradecanoyl phorbol 13-acetate (TPA), growth factors or stress stimuli, there is a considerable enhancement in c-Jun/AP-1 DNA binding and transcription activity (Lee et al., 1987; Sherman et al., 1990; Lamph et al., 1988; Ryder and Nathans, 1988; Quantin and Breathnach, 1988; Devary et al., 1991; Pertovaara et al., 1989). Enhanced AP-1 activity is accounted for in part by a rapid induction of c-Jun transcription. The newly synthesized c-Jun mRNA, however, decays quickly, with a short half-life that lasts for just 20-25 minutes. The c-Jun mRNA turnover is govern by an AU-rich RNA-destabilizing elements in the 3' untranslated region, an intrinsic activity that does not appear to be tightly coupled to ongoing translation by ribosomes and is insensitive to blockage of transcription (Peng et al., 1996). Exposure of cells to LTV, MCSF and photodynamic therapy increases c-Jun mRNA stability considerably, possibly due to the activation of RNA binding proteins by these stimuli (Kick et al., 1996; Blattner et al., 2000; Nakamura et al., 1991).

The stability of the c-Jun protein depends on its

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