Induction of proto-oncogene JUN/AP-1 by serum and TPA

Abstract

The response of a cell to mitogens and differentiation agents involves the transcriptional induction of several cellular genes. Prominent among these so-called 'immediate early' or 'competence' genes are the nuclear oncogenes fos and myc. Although the precise function of these early response genes in growth control is not understood, it is likely that many of them are involved in the transition from G0 to G1 in the cell cycle. The findings that the products of nuclear proto-oncogenes jun and erbA are transcriptional factors supports the notion of the role of the nuclear oncoproteins in the regulation of gene expression. Recently, it has been reported that the FOS protein is associated in transcriptional complexes with the product of the jun oncogene, the transcription factor AP-1. As the fos gene is induced in response to mitogens during initiation of cell growth, we investigated whether expression of the nuclear transcription factor AP-1 is also inducible. We report that mouse c-jun gene transcription is rapidly induced by serum and phorbol-ester 12-o-tetradecanoyl phorbol 13-acetate (TPA). Furthermore, induction is transient and the mRNA is superinduced by inhibitors of protein synthesis.

c-Jun, at the crossroad of the signaling network

“…These observations suggest the existence of a regulatory circuit, in which AP-1 can activate the c-Jun promoter and gene expression, whereas, expression of c-Jun in turn further enhances AP-1 thereby potentiating its own gene promoter activation ( Fig. 1) (Angel et al, 1988b;Lamph et al, 1988;Nakamura et al, 1991). Such an autocrine and feed-forward mechanism allows c-Jun to not only prolong AP-1 activity, but also amplify it.…”

“…Initiation of this process begins with stimulus activated signal transduction cascades that lead to a rapid change in the phosphorylation state of c-Jun. This event takes place on the pre-existing c-Jun, within minutes of stimulus treatment, and is independent of de novo protein synthesis (Lamph et al, 1988;Bohmann, 1990;Papavassiliou et al, 1992).…”

Expression of human p53 requires synergistic activation of transcription from the p53 promoter by AP-1, NF-κB and Myc/Max

“…We therefore examined binding of nuclear proteins from HeLa tk 7 cells to the p53-AP-1 motif in comparison with the coll-TRE in gel retardation assays after antibody perturbation with anti c-Fos or anti c-Jun antibodies ( Figure 3). Prior to the preparation of the nuclear extracts, the HeLa tk 7 cells were treated with TPA for 24 h to activate the AP-1 (Lee et al, 1987, Angel et al, 1987, Lamph et al, 1988 and NF-kB (Sen andBaltimore, 1986, Bohnlein et al, 1988) transcription factors. Up to ®ve shifted complexes appeared in case of the putative AP-1 motif from the hp53-promoter (complexes`a ± e' in Figure 3a).…”

Opposing activities of c-Fos and Fra-2 on AP-1 regulated transcriptional activity in mouse keratinocytes induced to differentiate by calcium and phorbol esters

“…The simultaneous addition of calcium and TPA to the cells resulted in levels of AP-1-CAT activity that were intermediate between those in 0.12 mM calcium and 162 nM TPA (data not shown). TPA-inducible AP-1-CAT activity has been attributed to the induction, and/or modification of c-Fos and c-Jun (Greenberg and Zi , 1984;Lamph et al, 1988;Devary et al, 1991). To establish whether c-Fos plays a role in TPA-mediated AP-1-CAT activity in keratinocytes, AP-1 transcriptional activity was evaluated in c-fos null keratinocytes treated with TPA.…”