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.
Department of Microbiology and Immunology, Cancer Research Center, Faculty of Health Sciences, Ben Gurion University of the Negev, Beer Sheva 84105, Israel.
Y
Y
Schavinsky-Khrapunsky
M
M
Huleihel
M
M
Aboud
A
A
Torgeman
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