Related Experiment Videos
Yeast PKA represses Msn2p/Msn4p-dependent gene expression to regulate growth, stress response and glycogen
1Department of Biochemistry, Duke University Medical Center, Durham, NC 27710, USA.
Abstract:
Yeast cAMP-dependent protein kinase (PKA) activity is essential for growth and antagonizes induction of the general stress response as well as accumulation of glycogen stores. Previous studies have suggested that the PKA effects on the two latter processes result in part from transcription repression. Here we show that transcription derepression that accompanies PKA depletion is dependent upon the presence of two redundant Zn2+-finger transcription factors, Msn2p and Msn4p. The Msn2p and Msn4p proteins were shown previously to act as positive transcriptional factors in the stress response pathway, and our results suggest that Msn2p and Msn4p also mediate PKA-dependent effects on stress response as well as glycogen accumulation genes. Interestingly, PKA activity is dispensable in a strain lacking Msn2p and Msn4p activity. Thus, Msn2p and Msn4p may antagonize PKAdependent growth by stimulating expression of genes that inhibit growth. In agreement with this model, Msn2p/Msn4p function is required for expression of a gene, YAK1, previously shown to antagonize PKA-dependent growth. These results suggest that Msn2p/Msn4p-dependent gene expression may account for all, or at least most, of the pleiotropic effects of yeast PKA, including growth regulation, response to stress and carbohydrate store accumulation.
Insights
Yeast protein kinase A (PKA) regulates stress response and glycogen storage. Two transcription factors, Msn2p and Msn4p, mediate these PKA effects, controlling growth and stress genes.
Area of Science:
- Molecular Biology
- Yeast Genetics
- Signal Transduction
Background:
- Yeast cAMP-dependent protein kinase (PKA) activity is crucial for growth.
- PKA antagonizes the general stress response and glycogen accumulation.
- Previous research indicated PKA influences these processes via transcriptional repression.
Purpose of the Study:
- To investigate the role of transcription factors in PKA-mediated regulation.
- To identify the specific factors responsible for PKA's effects on stress response and glycogen metabolism.
- To elucidate the mechanism by which PKA influences yeast growth.
Main Methods:
- Analysis of gene expression in yeast strains with varying PKA and transcription factor activity.
- Gene deletion studies to assess the redundancy of Msn2p and Msn4p.
- Examination of PKA's dispensability in Msn2p/Msn4p-deficient strains.
Main Results:
- Transcription derepression upon PKA depletion depends on Msn2p and Msn4p.
- Msn2p and Msn4p mediate PKA's effects on stress response and glycogen accumulation genes.
- PKA activity is dispensable in yeast lacking Msn2p and Msn4p.
- Msn2p/Msn4p are required for the expression of YAK1, a gene that inhibits PKA-dependent growth.
Conclusions:
- Msn2p and Msn4p are key mediators of PKA's pleiotropic effects in yeast.
- These transcription factors likely antagonize PKA-dependent growth by upregulating inhibitory genes.
- Msn2p/Msn4p-dependent gene expression accounts for PKA's regulation of growth, stress response, and carbohydrate storage.