Transcriptional and posttranscriptional control of c-fos gene expression in human monocytes

Journal Article · Fri Jan 01 04:00:00 EST 1988 · Mol. Cell. Biol.; (United States)

DOI:https://doi.org/10.1128/MCB.8.1.340· OSTI ID:7077582

Sariban, E; Luebbers, R; Kufe, D

The authors examined the mechanisms that are responsible for the regulation of c-fos gene expression in human monocytes. Levels of c-fos mRNA were low or undetectable in resting monocytes. Results of run-on transcription assays, however, demonstrated that both the first two and last two exons of the c-fos gene were transcribed at similar rates, and that only the sense strand of this gene was transcribed. These findings suggest that the level of c-fos transcripts in resting human monocytes is controlled at a posttranscriptional level. Activation of resting monocytes with phorbol ester was associated with a rapid and transient increase in c-fos mRNA levels. This increase in c-fos transcripts was related to an enhanced rate of c-fos transcription. Moreover, exposure of resting monocytes to inhibitors of protein synthesis induced (i) a rapid and marked (300-fold) increase in c-fos mRNA levels, despite only a 9-fold increase in c-fos transcription, and (ii) a prolongation of the half-life of c-fos mRNA. Thus, while posttranscriptional control was responsible for the down-regulation of c-fos transcripts in both resting and activated human monocytes, transcriptional mechanisms were responsible for the transient increase in c-fos expression induced by phorbol ester. Furthermore, the marked increases in c-fos mRNA associated with inhibition of protein synthesis were regulated by both transcriptional and posttranscriptional mechanisms. These findings may be related to recent observations which indicate that both positive and negative factors transcriptionally regulate c-fos gene expression and that sequences found in the 3'-untranslated region of the c-fos mRNA are responsible for the stability of this transcript.

• Research Organization: Lab. of Clinical Pharmacology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA (US)
• OSTI ID: 7077582
• Journal Information: Mol. Cell. Biol.; (United States), Journal Name: Mol. Cell. Biol.; (United States) Vol. 8:1; ISSN MCEBD
• Country of Publication: United States
• Language: English

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59 BASIC BIOLOGICAL SCIENCES
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
BIOLOGICAL MATERIALS
BIOLOGICAL PATHWAYS
BLOOD
BLOOD CELLS
BODY FLUIDS
CARCINOGENS
ENZYME INHIBITORS
ESTERS
GENE REGULATION
GENES
GROWTH FACTORS
HALF-LIFE
LEUKOCYTES
MATERIALS
MESSENGER-RNA
MITOGENS
MONOCYTES
NUCLEIC ACIDS
NUCLEOPROTEINS
ONCOGENES
ORGANIC COMPOUNDS
PHENOTYPE
PHORBOL ESTERS
POST-TRANSLATION MODIFICATION
PROTEINS
RNA
TRANSCRIPTION FACTORS