INDUCTION OF CELL-GROWTH REGULATORY GENES BY P53

Transcriptionally regulated growth-response genes play a pivotal role in the determination of the fate of a cell. p53 is known to transcript ionally regulate genes important in regulating cell growth potential. Using differential reverse transcription-PCR analysis of rat embryo fi broblast cells containing a temperature-sensitive p53 allele, we were able to isolate several transcripts up-regulated specifically in cells harboring functional p53 protein. Two of these genes, SM20 and micros omal epoxide hydrolase (mEH), are previously described genes. Two prev iously uncharacterized cDNAs, cell growth regulatory (CGR) genes CGR11 and CGR19, were isolated. The predicted amino acid sequence of these novel proteins contain known motifs; EF-hand domains (CGR11) and a rin g-finger domain (CGR19), suggestive of function. CGR11 and CGR19 appea r to be primary response genes expressed to moderate levels in functio nal p53 cells. Both CGR11 and CGR19 are able to inhibit the growth of several cell lines.