MSI1 suppresses hyperactive RAS via the cAMP-dependent protein kinase and independently of chromatin assembly factor-1 |
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Authors: | Xiaoyan Zhu Nadine Démolis Michel Jacquet Tamar Michaeli |
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Institution: | (1) Department of Developmental and Molecular Biology, Albert Einstein College of Medicine, Bronx, NY 10461, USA e-mail: michaeli@aecom.yu.edu, US;(2) Laboratorie Information Génétique et Dévelopment, Institut de Génétique et Microbiologie, URA CNRS 2225, Université Paris-Sud, 91405 Orsay Cedex, France, FR |
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Abstract: | 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.
Received: 23 August 1999 / Accepted: 7 April 2000 |
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Keywords: | RAS MSI1/CAC3 CAF-1 BCY1/PKA |
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