PT  - JOURNAL ARTICLE
AU  - Rishi, Arun K.
AU  - Hsu, C. K. Alex
AU  - Li, Xiao-Su
AU  - Hussain, Arif
AU  - Gerald, Tonya M.
AU  - Fontana, Joseph A.
TI  - Transcriptional Repression of the Cyclin-dependent Kinase Inhibitor p21<sup>WAF1/CIP1</sup> Gene Mediated by <em>cis</em> Elements Present in the 3′-Untranslated Region
DP  - 1997 Nov 15
TA  - Cancer Research
PG  - 5129--5136
VI  - 57
IP  - 22
4099  - http://cancerres.aacrjournals.org/content/57/22/5129.short
4100  - http://cancerres.aacrjournals.org/content/57/22/5129.full
SO  - Cancer Res1997 Nov 15; 57
AB  - The cyclin-dependent kinase inhibitor p21WAF1/CIP1 plays a major role in the induction of G1 cell cycle arrest following DNA damage and is known to be regulated by p53-dependent and -independent pathways. Here, we show that p21WAF1/CIP1 transcription is also regulated, independently of p53, by the cis elements that are located downstream of the transcription start site. A cDNA fragment of ∼180 bp, located 260 bases 3′ to the translation termination codon of p21WAF1/CIP1 cDNA, was cloned in both the sense and antisense orientations downstream of the CMV promoter, upstream of the SV40 promoter, and both upstream and downstream of the p21WAF1/CIP1 promoter in the plasmids carrying the luciferase reporter gene. The constructs were transiently transfected in human breast carcinoma cells MCF-7 and MDA-MB-468 and a Syrian hamster smooth muscle cell line DDT1MF2 and were found to elicit 2–3-fold or higher repression of luciferase activities. By using overlapping deletions of the above 180-bp fragment, we identified a 48-bp subfragment that contains putative cis element(s) that participate in the transcriptional repression of the p21WAF1/CIP1 gene. The overlapping subfragments bind, in vitro, to specific proteins present in the nuclear extracts of MDA-MB-468 and DDT1MF2 cells. We, therefore, propose that additional mechanism(s) exist that regulate expression of the cellular p21waf1/cip1 and may contribute to p21WAF1/CIP1-dependent control of the cell cycle. ©1997 American Association for Cancer Research.