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Comparison of bax , waf1 , and IMP dehydrogenase regulation in response to wild‐type p53 expression under normal growth conditions
Author(s) -
Liu Yuan,
Riley Lee B.,
Bohn Shirley A.,
Boice Judith A.,
Stadler Patrizia B.,
Sherley James L.
Publication year - 1998
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/(sici)1097-4652(199811)177:2<364::aid-jcp18>3.0.co;2-9
Subject(s) - downregulation and upregulation , biology , oxidoreductase , cell growth , nad+ kinase , dehydrogenase , gene , gene expression , microbiology and biotechnology , enzyme , biochemistry
Recently, we demonstrated that downregulation of inosine‐5′‐monophosphate dehydrogenase (IMPD; IMP:NAD oxidoreductase, EC 1.2.1.14), the rate‐limiting enzyme for guanine nucleotide biosynthesis, is required for p53‐dependent growth suppression. These studies were performed with cell lines derived from immortal, nontumorigenic fibroblasts that express wild‐type p53 conditionally by virtue of a metal‐responsive promoter. Here, the p53‐dependent properties of the original “p53‐inducible” fibroblasts are presented in detail and compared to related properties of epithelial cells that also express wild‐type p53 conditionally, but by virtue of a temperature‐responsive promoter. Both types of p53‐inducible cells were designed to approximate normal physiologic relationships between the host cell and the regulated p53 protein. Together, they were used to investigate expression relationships between IMPD and other p53‐responsive genes proposed as mediators of p53‐dependent growth suppression. In both types of cells, IMPD activity, protein, and mRNA were consistently coordinately reduced in response to p53 expression. In contrast, mRNAs for waf1 , bax , and mdm2 showed disparate patterns of expression, being induced in one conditional cell type, but not the other. This distinction in regulation pattern suggests that under normal growth conditions, unlike IMPD downregulation, bax and waf1 induction is not a rate‐determining event for p53‐dependent growth suppression. J. Cell. Physiol. 177:364–376, 1998. © 1998 Wiley‐Liss, Inc.