Activation of the p21Waf1/Cip1Promoter by theetsOncogene Family Transcription Factor E1AF

Altered Ets transcription factor activity in prostate tumor cells inhibits anchorage-independent growth, survival, and invasiveness

“…This induction of p21 cip expression by either Ets2 construct may be partially responsible for the reduced growth rate of PPC-1 cells expressing these constructs (Figure 1b). We have not yet identi®ed essential Ets binding sites in the p21 promoter, but neither of the two previously characterized upstream overlapping Ets/p53 binding sites at approximately 72.2 kb and 71.3 k (Funaoka et al, 1997;Beier et al, 1999) are present in the 4-Luc reporter. In addition, PPC-1 cells are reported to contain only mutant p53 (Borner et al, 1995), so interaction with p53 is an unlikely mechanism for the Ets2 constructs in regulating p21 expression in these cells.…”

“…Expression of p21 Cip is activated by hyperstimulation of the Ras/Raf signaling pathway (Woods et al, 1997), and p21 Cip has been reported to be a direct transcriptional target of overexpressed Ets factor E1AF (Funaoka et al, 1997). We measured the steady-state levels of p21 Cip and the related p27 Kip1 protein in the stable cell lines using immunoblot analysis (Figure 4).…”

Signal transduction and the Ets family of transcription factors

“…Fli1 is known to control the transcription of the retinoblastoma protein, Rb, a critical cell cycle regulator (Tamir et al, 1999). Other important regulators of the G1 to S transition, such as cyclin D1, cdc2 and p21 are known to contain functional Ets binding sites within their promoter regions (Albanese et al, 1995;Funaoka et al, 1997;Wen et al, 1995). Additionally, Ets1 is known to be hyperphosphorylated during mitosis (Fleischman et al, 1993).…”

Ras induces p21Cip1/Waf1 cyclin kinase inhibitor transcriptionally through Sp1-binding sites

“…Besides p53, transcription factor Ap-2 (Zeng et al, 1997), E2F-1/DP-1 complex (Hiyama et al, 1997), E2A (Prabhu et al, 1997), an ets-oncogene related E1AF (Funaoka et al, 1997), C/EBP , RAR (Liu et al, 1996a), VDR (Liu et al, 1996b), STATs (Chin et al, 1996), and Sp1 family (Biggs et al, 1996;Li et al, 1998;Owen et al, 1998;Prowse et al, 1997;Yan and Zi , 1997) are known to stimulate p21 promoter activity. Our results show that Ras induces p21 transcriptionally and that the Ras-responsive region in p21 promoter spans a short region downstream of the nucleotide 7110 relative to the transcription start site.…”