Masters Theses

Junseo Oh

Date of Award

12-1991

Degree Type

Thesis

Degree Name

Master of Science

Major

Biochemistry and Cellular and Molecular Biology

Major Professor

Wesley D. Wicks

Committee Members

J. Koontz, D. Roberts

Abstract

It is known that the transcriptional rate of two of the cAMP-responsive genes, phosphoenolpyruvate carboxykinase (PEPCK) and tyrosine aminotransferase (TAT), is stimulated by cAMP in rat hepatoma cells and consequently their mRNA levels are increased, reaching a maximum within 2 hours. However, in both cases the mRNA levels decline after the peak (deinduction) due to unknown mechanisms. The kinetics of induction of mRNA and mRNATAT by cAMP have been studied in the present report, and it was demonstrated that, in spite of the superficially similar effects of cAMP on both genes, the mechanisms of deinduction are not the same; that is, the decline in the mRNATAT level is due to cAMP metabolism, whereas the decline in mRNAPEPCK is caused by some kind of desensitization process which appears to involve delayed inhibition of the initial stimulation of PEPCK gene transcription. Considering the multiplicity of CREB(CRE binding) / ATF (activating transcription factor) proteins and the important differences found in the location and sequences of the PEPCK and TAT CRE's (cAMP regulatory element), the differences in the mechanism of deinduction raises a question as to whether or not different CREB's might mediate the effects of cAMP on these two different genes in the same cell. From analysis of the effects of cycloheximide on cAMP inducibility, it appears that the effects of cAMP on mRNAPEPCK and mRNATAT are direct and that the protein factor mediating cAMP action on PEPCK differs from that regulating TAT, at least in terms of its stability.

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