TPA activates p21WAF-1 promoter in human T-cells through its second most upstream Sp1 site.
The p21(WAF-1) promoter contains binding sites for a number of transcription factors which mediate its activation by a variety of external signals. Moreover, it has been reported that the transcription factors involved in p21(WAF-1) activation by certain signaling factors, like the phorbol ester TPA, may vary in different cell types. We were interested in elucidating the mechanism of p21(WAF-1) activation by TPA in human T-cells, since this activation could explain the antagonistic effect of PKC on apoptosis induction in these cells noted in our previous studies. Using the Jurkat human T-cells we found that TPA activated p21(WAF-1) expression by a PKC-dependent mechanism and that out of six Sp1 binding sites residing in its promoter the second most upstream one was critically essential for this activation. Since p21(WAF-1) is known to inhibit the onset of apoptosis, its PKC-dependent activation may likely account for the PKC antagonistic effect on apoptosis induction in these cells.
Schavinsky-Khrapunsky
Y
Y
Department of Microbiology and Immunology, Cancer Research Center, Faculty of Health Sciences, Ben Gurion University of the Negev, Beer Sheva 84105, Israel.
Huleihel
M
M
Aboud
M
M
Torgeman
A
A
D001665:Binding Sites; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000235:genetics* / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000378:metabolism; D006801:Humans; D019169:Jurkat Cells; D011401:Promoter Regions, Genetic; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism; D011494:Protein Kinases / Q000378:metabolism; D013601:T-Lymphocytes / Q000187:drug effects* / Q000502:physiology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D015533:Transcriptional Activation
C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D004268:DNA-Binding Proteins; D004791:Enzyme Inhibitors; D011494:Protein Kinases; C065999:Sp1 kinase; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate