1998/01/01 by Yuan Liu, Shirley A. Bohn, James L. Sherley · 1 voice
Biochemistry, Genetics and Molecular Biology · Medicine · #Biochemical and Molecular Research #Cytomegalovirus and herpesvirus research #RNA modifications and cancer
paper · doi:10.1091/mbc.9.1.15
openalex publication_date 1998/01/01 · openalex created_date 2025/10/10 · openalex updated_date 2026/06/24
We have proposed that reduced activity of inosine-5'-monophosphate dehydrogenase (IMPD; IMP:NAD oxidoreductase, EC 1.2.1.14), the rate-limiting enzyme for guanine nucleotide biosynthesis, in response to wild-type p53 expression, is essential for p53-dependent growth suppression. A gene transfer strategy was used to demonstrate that under physiological conditions constitutive IMPD expression prevents p53-dependent growth suppression. In these studies, expression of bax and waf1, genes implicated in p53-dependent growth suppression in response to DNA damage, remains elevated in response to p53. These findings indicate that under physiological conditions IMPD is a rate-determining factor for p53-dependent growth regulation. In addition, they suggest that the impd gene may be epistatic to bax and waf1 in growth suppression. Because of the role of IMPD in the production and balance of GTP and ATP, essential nucleotides for signal transduction, these results suggest that p53 controls cell division signals by regulating purine ribonucleotide metabolism.