Regulation of IMP dehydrogenase gene expression by its end products, guanine nucleotides

Journal Article · Fri Nov 01 04:00:00 EST 1991 · Molecular and Cellular Biology; (United States)

DOI:https://doi.org/10.1128/MCB.11.11.5417· OSTI ID:5089854

Glesne, D A; Huberman, E ^[1]; Collart, F R ^[2]

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1. Argonne National Lab., IL (United States) Univ. of Chicago, IL (United States)
2. Argonne National Lab., IL (United States)

To study the regulation of IMP dehydrogenase (IMPDH), the rate-limiting enzyme of guanine nucleotide biosynthesis. The authors examined the effects of nucleosides, nucleotides, nucleotide analogs, for the IMPDH inhibitor mycophenolic acid (MPA) on the steady-state levels of IMPDH mRNA. The results indicated that IMPDH gene expression is regulated inversely by the intracellular level of guanine ribonucleotides and subsequently reduced IMPDH steady-state mRNA levels in a time- and dose-dependent manner. Conversely, MPA treatment diminished the level of guanine ribonucleotides and increased IMPDH mRNA levels. Both of these effects on the steady-state level of IMPDH mRNA could be negated by cotreatment with guanosine and MPA. The down regulation of IMPDH gene expression by guanosine or its up regulation by MPA was not due to major changes in transcriptional initiation and elongation or mRNA stability in the cytoplasm but rather was due to alterations in the levels of IMPDH mRNA in the nucleus. These results suggest that IMPDH gene expression is regulated by posttranscriptional, nuclear event in response to fluctuations in the intracellular level of guanine ribonucleotides.

• DOE Contract Number: W-31109-ENG-38
• OSTI ID: 5089854
• Journal Information: Molecular and Cellular Biology; (United States), Journal Name: Molecular and Cellular Biology; (United States) Vol. 11:11; ISSN MCEBD; ISSN 0270-7306
• Country of Publication: United States
• Language: English

Related Subjects

550200* -- Biochemistry
59 BASIC BIOLOGICAL SCIENCES
AMINES
AROMATICS
AZAARENES
ENZYME INHIBITORS
ENZYMES
GENE REGULATION
GUANINE
HEMIACETAL DEHYDROGENASES
HETEROCYCLIC COMPOUNDS
HYDROXY COMPOUNDS
MESSENGER-RNA
NUCLEIC ACIDS
NUCLEOSIDES
NUCLEOTIDES
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
OXIDOREDUCTASES
PHENOLS
POST-TRANSLATION MODIFICATION
PROTEINS
PURINES
RIBOSIDES
RNA
TRANSCRIPTION