The novel yeast PAS kinase Rim 15 orchestrates G0-associated antioxidant defense mechanisms.
The highly conserved PKA and TOR proteins define key signaling pathways that control cell proliferation in response to growth factors and/or nutrients. In yeast, inactivation of PKA and/or TOR causes cells to arrest growth early G1 and induces a program that is characteristic of G0 cells. We have recently shown that the protein kinase Rim15 integrates both PKA- and TOR-mediated signals. In this work, we demonstrate that the Rim15-activated genomic expression program following glucose limitation at the diauxic shift is mediated by the three transcription factors Gis1, Msn2, and Msn4. The Rim15 regulon comprises several gene clusters implicated in the adaptation to respiratory growth, including classical oxidative stress genes such as SOD1 and SOD2, suggesting that the reduced life span of rim15delta cells may be due to their deficiency in oxidative damage prevention. Interestingly, we found that the primary amino acid sequence of Rim15 includes in its amino-terminal part a conserved PAS domain, known to act as a sensor for a variety of stimuli, We propose that Rim15 has evolved to integrate nutrient signals (transduced via TOR and PKA) and redox and/or oxidative stress signals to appropriately induce a transcriptional program that ensures survival in G0.
Department of Microbiology and Molecular Medicine, Centre Médical Universitaire, Univeristy of Geneva, Switzerland.
Elisabetta
E
Cameroni
Nicolas
N
Hulo
Johnny
J
Roosen
Joris
J
Winderickx
Claudio
C
De Virgilio
D000595:Amino Acid Sequence; D000975:Antioxidants / Q000494:pharmacology*; D015152:Blotting, Northern; D002470:Cell Survival; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D018076:DNA, Complementary / Q000378:metabolism; D016193:G1 Phase; D005786:Gene Expression Regulation; D005947:Glucose / Q000378:metabolism; D008954:Models, Biological; D008969:Molecular Sequence Data; D009693:Nucleic Acid Hybridization; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D010100:Oxygen / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000378:metabolism; D011494:Protein Kinases / Q000502:physiology*; D017434:Protein Structure, Tertiary; D012333:RNA, Messenger / Q000378:metabolism; D016192:Resting Phase, Cell Cycle; D012441:Saccharomyces cerevisiae / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism / Q000502:physiology*; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction
D000975:Antioxidants; D017868:Cyclic AMP-Dependent Protein Kinases; D018076:DNA, Complementary; D005947:Glucose; D010100:Oxygen; D019869:Phosphatidylinositol 3-Kinases; D017853:Phosphotransferases (Alcohol Group Acceptor); D011494:Protein Kinases; D012333:RNA, Messenger; D029701:Saccharomyces cerevisiae Proteins; C410736:Rim15 protein, S cerevisiae; C083324:TOR1 protein, S cerevisiae