TY - JOUR
T1 - WAF1, a potential mediator of p53 tumor suppression
AU - El-Deiry, Wafik S.
AU - Tokino, Takashi
AU - Velculescu, Victor E.
AU - Levy, Daniel B.
AU - Parsons, Ramon
AU - Trent, Jeffrey M.
AU - Lin, David
AU - Mercer, W. Edward
AU - Kinzler, Kenneth W.
AU - Vogelstein, Bert
N1 - Funding Information:
The authors thank David Hill and Marilee Burrell for preparing the mouse antisera to WAFI. This work was supported by the Preuss Foundation, the Clayton Fund, and National Institutes of Health grants CA-09071 and CA-43460. B. V. is an American Cancer Society research professor.
PY - 1993/11/19
Y1 - 1993/11/19
N2 - The ability of p53 to activate transcription from specific sequences suggests that genes induced by p53 may mediate its biological role as a tumor suppressor. Using a subtractive hybridization approach, we identified a gene, named WAF1, whose induction was associated with wild-type but not mutant p53 gene expression in a human brain tumor cell line. The WAF1 gene was localized to chromosome 6p21.2, and its sequence, structure, and activation by p53 was conserved in rodents. Introduction of WAF1 cDNA suppressed the growth of human brain, lung, and colon tumor cells in culture. Using a yeast enhancer trap, a p53-binding site was identified 2.4 kb upstream of WAF1 coding sequences. The WAF1 promoter, including this p53-binding site, conferred p53-dependent inducibility upon a heterologous reporter gene. These studies define a gene whose expression is directly induced by p53 and that could be an important mediator of p53-dependent tumor growth suppression.
AB - The ability of p53 to activate transcription from specific sequences suggests that genes induced by p53 may mediate its biological role as a tumor suppressor. Using a subtractive hybridization approach, we identified a gene, named WAF1, whose induction was associated with wild-type but not mutant p53 gene expression in a human brain tumor cell line. The WAF1 gene was localized to chromosome 6p21.2, and its sequence, structure, and activation by p53 was conserved in rodents. Introduction of WAF1 cDNA suppressed the growth of human brain, lung, and colon tumor cells in culture. Using a yeast enhancer trap, a p53-binding site was identified 2.4 kb upstream of WAF1 coding sequences. The WAF1 promoter, including this p53-binding site, conferred p53-dependent inducibility upon a heterologous reporter gene. These studies define a gene whose expression is directly induced by p53 and that could be an important mediator of p53-dependent tumor growth suppression.
UR - http://www.scopus.com/inward/record.url?scp=0027359827&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0027359827&partnerID=8YFLogxK
U2 - 10.1016/0092-8674(93)90500-P
DO - 10.1016/0092-8674(93)90500-P
M3 - Article
C2 - 8242752
AN - SCOPUS:0027359827
SN - 0092-8674
VL - 75
SP - 817
EP - 825
JO - Cell
JF - Cell
IS - 4
ER -