MSI1 suppresses hyperactive RAS via the cAMP-dependent protein kinase and independently of chromatin assembly factor-1.

RAS hyperactivation in the yeast Saccharomyces cerevisiae leads to multiple nutritional growth defects associated with overstimulation of the cAMP signaling pathway. Hyperactive RAS can be suppressed by overexpression of MSI1, a subunit of chromatin assembly factor-1 (yCAF-1). MSI1 overexpression suppresses phenotypes induced by increased cAMP content in multiple genetic backgrounds. ...
However, MSI1 does not inhibit cAMP synthesis or total cellular cAMP-dependent protein kinase (PKA) activity, nor does MSI1 stimulate expression of several cAMP-repressible genes critical for the acquisition of thermotolerance in the stationary phase. Our analysis indicates that yCAF-1 is dispensable for inhibition of hyperactive RAS by MSI1. We demonstrate that in the presence of the PKA regulatory subunit, BCY1, MSI1 inhibits phenotypes of a mutationally activated PKA catalytic subunit. These observations indicate that MSI1 affects PKA function in a BCY1-dependent manner via mechanisms other than direct overall inhibition of PKA catalytic activity. MSI1 appears to provide two distinct roles in chromatin modeling as a component of yCAF-1, and in the inhibition of RAS signaling by modulating PKA.
Mesh Terms:
Chromatin Assembly Factor-1, Chromosomal Proteins, Non-Histone, Cyclic AMP, Cyclic AMP-Dependent Protein Kinases, DNA-Binding Proteins, Fungal Proteins, Recombinant Proteins, Saccharomyces cerevisiae, Saccharomyces cerevisiae Proteins, Signal Transduction, Suppression, Genetic, ras Proteins
Curr. Genet.
Date: Aug. 01, 2000
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