- THIS ARTICLE
- Full Text
- Full Text (PDF)
-
All Versions of this Article:
genetics.105.052266v1
172/3/1477 most recent - Alert me when this article is cited
- Alert me if a correction is posted
- SERVICES
- Similar articles in this journal
- Similar articles in PubMed
- Alert me to new issues of the journal
- Download to citation manager
- Reprints & Permissions
- CITING ARTICLES
- Citing Articles via HighWire
- Citing Articles via Google Scholar
- GOOGLE SCHOLAR
- Articles by Krasley, E.
- Articles by Strich, R.
- Search for Related Content
- PUBMED
- PubMed Citation
- Articles by Krasley, E.
- Articles by Strich, R.
Originally published as Genetics Published Articles Ahead of Print on December 30, 2005.
Genetics, Vol. 172, 1477-1486, March 2006, Copyright © 2006
doi:10.1534/genetics.105.052266
Regulation of the Oxidative Stress Response Through Slt2p-Dependent Destruction of Cyclin C in Saccharomyces cerevisiae
Elizabeth Krasley*,1,
Katrina F. Cooper
,2,
Michael J. Mallory*,2,
Roland Dunbrack* and
Randy Strich*,3
* Institute for Cancer Research, Fox Chase Cancer Center, Philadelphia, Pennsylvania 19111 and Department of Biochemistry, Drexel University College of Medicine, Philadelphia, Pennsylvania 19102
3 Corresponding author: Department of Molecular Biology, UMDNJ School of Osteopathic Medicine, 345 Science Center, Two Medical Center Dr., Stratford, NJ 08084.
E-mail: strichra{at}umdnj.edu
The Saccharomyces cerevisiae C-type cyclin and its cyclin-dependent kinase (Cdk8p) repress the transcription of several stress response genes. To relieve this repression, cyclin C is destroyed in cells exposed to reactive oxygen species (ROS). This report describes the requirement of cyclin C destruction for the cellular response to ROS. Compared to wild type, deleting cyclin C makes cells more resistant to ROS while its stabilization reduces viability. The Slt2p MAP kinase cascade mediates cyclin C destruction in response to ROS treatment but not heat shock. This destruction pathway is important as deleting cyclin C suppresses the hypersensitivity of slt2 mutants to oxidative damage. The ROS hypersensitivity of an slt2 mutant correlates with elevated programmed cell death as determined by TUNEL assays. Consistent with the viability studies, the elevated TUNEL signal is reversed in cyclin C mutants. Finally, two results suggest that cyclin C regulates programmed cell death independently of its function as a transcriptional repressor. First, deleting its corepressor CDK8 does not suppress the slt2 hypersensitivity phenotype. Second, the human cyclin C, which does not repress transcription in yeast, does regulate ROS sensitivity. These findings demonstrate a new role for the Slt2p MAP kinase cascade in protecting the cell from programmed cell death through cyclin C destruction.
This article has been cited by other articles:
 |
|
 |
|
  T. J. Cohen, M. J. Mallory, R. Strich, and T.-P. Yao Hos2p/Set3p Deacetylase Complex Signals Secretory Stress through the Mpk1p Cell Integrity Pathway Eukaryot. Cell, July 1, 2008; 7(7): 1191 - 1199. [Abstract] [Full Text] [PDF]
|
|