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. (C) 2003 Elsevier Science (USA). All rights reserved.