Protein kinase A, TOR, and glucose transport control the response to nutrient repletion in Saccharomyces cerevisiae

School of Pharmacy, University of Wisconsin, Madison, WI 53705, USA.
Eukaryotic Cell (Impact Factor: 3.18). 03/2008; 7(2):358-67. DOI: 10.1128/EC.00334-07
Source: PubMed

ABSTRACT Nutrient repletion leads to substantial restructuring of the transcriptome in Saccharomyces cerevisiae. The expression levels of approximately one-third of all S. cerevisiae genes are altered at least twofold when a nutrient-depleted culture is transferred to fresh medium. Several nutrient-sensing pathways are known to play a role in this process, but the relative contribution that each pathway makes to the total response has not been determined. To better understand this, we used a chemical-genetic approach to block the protein kinase A (PKA), TOR (target of rapamycin), and glucose transport pathways, alone and in combination. Of the three pathways, we found that loss of PKA produced the largest effect on the transcriptional response; however, many genes required both PKA and TOR for proper nutrient regulation. Those genes that did not require PKA or TOR for nutrient regulation were dependent on glucose transport for either nutrient induction or repression. Therefore, loss of these three pathways is sufficient to prevent virtually the entire transcriptional response to fresh medium. In the absence of fresh medium, activation of the cyclic AMP/PKA pathway does not induce cellular growth; nevertheless, PKA activation induced a substantial fraction of the PKA-dependent genes. In contrast, the absence of fresh medium strongly limited gene repression by PKA. These results account for the signals needed to generate the transcriptional responses to glucose, including induction of growth genes required for protein synthesis and repression of stress genes, as well as the classical glucose repression and hexose transporter responses.

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Available from: Matthew Slattery, Jul 30, 2015
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    • "Finally, we found that a ceased flux through the PP pathway is the last stage of the adaptation, occurring only 6 h after glucose depletion, which is accompanied by a change in NADPH source (Figure 5, 'III'). Moreover, we identify several reactions in the metabolic network (Figure 5, 'Regulatory site'), whose regulation most likely causes the observed changes in flux distribution (Figure 5, 'Fluxes') and the influence of metabolites levels Figure 5 Time-course reconstruction of the different events that lead to the adaptation based on the results presented in this report (regular text and solid arrows) and also supported by studies that were previously published (italics and dashed arrows) (Boy-Marcotte et al, 1996, 1998; DeRisi et al, 1997; Vincent and Carlson, 1998; Haurie et al, 2001; Haurie et al, 2004; Brauer et al, 2005; Radonjic et al, 2005; Slattery et al, 2008). "
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    Molecular Systems Biology 04/2013; 9:651. DOI:10.1038/msb.2013.11 · 14.10 Impact Factor
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    • "Furthermore, cAMP was able to produce similar transcriptional responses to those produced by N or P repletion. We have previously observed very similar results with G repletion (Slattery et al. 2008). "
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    • "The nucleocytoplasmic distributions of active Snf1 complexes provide versatility to the physiological response and adaptation to alternative carbon sources. The Snf1p, cAMP-dependent PKA and TOR kinase pathways regulate translation and various other cellular processes in an interdependent manner (Zurita-Martinez and Cardenas, 2005; Slattery et al., 2008; Busti et al., 2010). In addition to protein kinases, ribosome-associated proteins like Stm1p regulate translation in response to nutrient deprivation. "
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