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 transcriptionally regulate genes important in regulating cell growth potential. Using differential reverse transcription-PCR analysis of rat embryo fibroblast 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 microsomal epoxide hydrolase (mEH), are previously described genes. Two previously 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 ring-finger domain (CGR19), suggestive of function. CGR11 and CGR19 appear to be primary response genes expressed to moderate levels in functional p53 cells. Both CGR11 and CGR19 are able to inhibit the growth of several cell lines.
Madden
S L
SL
Department of Molecular and Cellular Biology, PharmaGenics, Inc., Allendale, New Jersey 07401, USA.
Galella
E A
EA
Riley
D
D
Bertelsen
A H
AH
Beaudry
G A
GA
D000595:Amino Acid Sequence; D000818:Animals; D002135:Calcium-Binding Proteins / Q000096:biosynthesis / Q000737:chemistry / Q000235:genetics*; D002455:Cell Division / Q000235:genetics*; D018076:DNA, Complementary / Q000235:genetics; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D005786:Gene Expression Regulation; D005809:Genes, Regulator; D016158:Genes, p53; D006131:Growth Inhibitors / Q000096:biosynthesis / Q000737:chemistry / Q000235:genetics*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008969:Molecular Sequence Data; D014176:Protein Biosynthesis; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000737:chemistry / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics / Q000302:isolation & purification; D051381:Rats; D011994:Recombinant Proteins / Q000378:metabolism; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D013045:Species Specificity; D013382:Subtraction Technique; D013696:Temperature; D016159:Tumor Suppressor Protein p53 / Q000502:physiology*
C103094:CGREF1 protein, human; C103095:CGRRF1 protein, human; D002135:Calcium-Binding Proteins; D018076:DNA, Complementary; D006131:Growth Inhibitors; D047908:Intracellular Signaling Peptides and Proteins; D011506:Proteins; D012333:RNA, Messenger; D011994:Recombinant Proteins; D016159:Tumor Suppressor Protein p53