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

Curr Genet. 2000 Aug;38(2):60-70. doi: 10.1007/s002940000133.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Chromatin Assembly Factor-1
  • Chromosomal Proteins, Non-Histone*
  • Cyclic AMP / metabolism
  • Cyclic AMP-Dependent Protein Kinases / metabolism*
  • DNA-Binding Proteins / metabolism*
  • Fungal Proteins / genetics
  • Fungal Proteins / metabolism*
  • Recombinant Proteins / metabolism
  • Saccharomyces cerevisiae / physiology*
  • Saccharomyces cerevisiae Proteins*
  • Signal Transduction
  • Suppression, Genetic
  • ras Proteins / metabolism*


  • Chromatin Assembly Factor-1
  • Chromosomal Proteins, Non-Histone
  • DNA-Binding Proteins
  • Fungal Proteins
  • MSI1 protein, S cerevisiae
  • Recombinant Proteins
  • Saccharomyces cerevisiae Proteins
  • Cyclic AMP
  • Cyclic AMP-Dependent Protein Kinases
  • ras Proteins