title: Mtl1 is required to activate general stress response through Tor1 and Ras2 inhibition under conditions of glucose starvation and oxidative stress.
abstract: Mtl1 is a member of the cell wall integrity (CWI) pathway of Saccharomyces cerevisiae, which functions as a cell wall sensor for oxidative stress. Genome-wide transcriptional analysis revealed a cluster of genes that were down-regulated in the absence of Mtl1. Many of these genes were potentially regulated by the general stress response factor Msn2/Msn4. In response to rapamycin, caffeine, glucose starvation and oxidative stress provoked by H(2)O(2), mtl1 presents a significant loss of viability as well as a deficiency in the transcriptional response mediated by Msn2/Msn4. The Mtl1 function was required (i) to induce ribosomal gene repression, (ii) to induce the general stress response driven by the transcription factor Msn2/Msn4, and (iii) to activate the CWI pathway in response to both glucose starvation and oxidative stress. We also detected higher cAMP levels in the mtl1 mutant than in wild type cells indicative of up-regulated RAS2-PKA activity. Disruption of TOR1, disruption of RAS2, or hyperactivation of Rho1 restored both the viability and the transcriptional function (both ribosomal and Msn2/Msn4-dependent gene expression) in the mtl1 mutant to almost wild type levels when cells were starved of glucose or stressed with H(2)O(2). Taking our results together, we propose an essential role for Mtl1 in signaling oxidative stress and quiescence to the CWI pathway and to the general stress response through Rho1 and the inhibition of either the TOR1 or RAS2 functions. These mechanisms would be required to allow cells to adapt to both oxidative and nutritional stresses.
authors.affiliation: Departament de Ciències Mèdiques Bàsiques-IRBLleida, Facultad de Medicina, Universidad de Lleida, Lleida 25008, Spain.
authors.forename: Mima Ivanova
authors.initials: MI
authors.lastname: Petkova
authors.forename: Nuria
authors.initials: N
authors.lastname: Pujol-Carrion
authors.forename: Javier
authors.initials: J
authors.lastname: Arroyo
authors.forename: Jesús
authors.initials: J
authors.lastname: García-Cantalejo
authors.forename: Maria
authors.initials: M
authors.lastname: Angeles de la Torre-Ruiz
mesh_terms: D002473:Cell Wall / Q000378:metabolism; D004247:DNA / Q000378:metabolism; D005656:Fungal Proteins / Q000378:metabolism; D015966:Gene Expression Regulation, Fungal; D005947:Glucose / Q000378:metabolism*; D020935:MAP Kinase Signaling System; D008954:Models, Biological; D020411:Oligonucleotide Array Sequence Analysis; D018384:Oxidative Stress; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism*; D015398:Signal Transduction; D014157:Transcription Factors / Q000378:metabolism; D018631:ras Proteins / Q000378:metabolism*; D020741:rho GTP-Binding Proteins / Q000378:metabolism*
chemical_list: D004247:DNA; D005656:Fungal Proteins; D005947:Glucose; D019869:Phosphatidylinositol 3-Kinases; D011956:Receptors, Cell Surface; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors; D018631:ras Proteins; D020741:rho GTP-Binding Proteins; C101654:Mtl-1 protein, Cryptococcus neoformans; C550933:Mtl1 protein, S cerevisiae; C083324:TOR1 protein, S cerevisiae; C489015:RAS2 protein, S cerevisiae; C051302:RHO1 protein, S cerevisiae
references.citation: Curr Genet. 2006 May;49(5):281-93
references.pmid: 16397762
references.citation: FEMS Microbiol Rev. 2000 Oct;24(4):469-86
references.pmid: 10978547
references.citation: Biochim Biophys Acta. 2008 Feb;1780(2):179-84
references.pmid: 17980162
references.citation: Microbiology (Reading). 2000 Sep;146 ( Pt 9):2113-2120
references.pmid: 10974099
references.citation: Genes Dev. 1998 Feb 15;12(4):586-97
references.pmid: 9472026
references.citation: Proc Natl Acad Sci U S A. 1996 Jun 11;93(12):5777-82
references.pmid: 8650168
references.citation: Mol Cell. 2002 Sep;10(3):457-68
references.pmid: 12408816
references.citation: Cell. 1985 Jan;40(1):27-36
references.pmid: 2981630
references.citation: J Biol Chem. 2006 Dec 29;281(52):39785-95
references.pmid: 17088254
references.citation: Yeast. 1985 Sep;1(1):25-38
references.pmid: 2851899
references.citation: J Biol Chem. 2009 May 8;284(19):12604-8
references.pmid: 19299514
references.citation: J Biol Chem. 2004 Nov 5;279(45):46527-35
references.pmid: 15326168
references.citation: Trends Genet. 1991 Jan;7(1):28-33
references.pmid: 1848378
references.citation: Yeast. 1994 Dec;10(13):1753-90
references.pmid: 7747517
references.citation: Genetics. 2002 Oct;162(2):663-76
references.pmid: 12399379
references.citation: EMBO J. 2002 Jan 15;21(1-2):135-44
references.pmid: 11782433
references.citation: Mol Cell Biol. 2004 Jan;24(1):338-51
references.pmid: 14673167
references.citation: EMBO J. 1997 Dec 1;16(23):7196-206
references.pmid: 9384596
references.citation: Mol Cell Biol. 2006 Jul;26(13):4853-62
references.pmid: 16782874
references.citation: Eukaryot Cell. 2005 Jan;4(1):63-71
references.pmid: 15643061
references.citation: Curr Biol. 2002 Apr 2;12(7):588-93
references.pmid: 11937029
references.citation: Bioessays. 1995 Nov;17(11):959-65
references.pmid: 8526890
references.citation: Nature. 1999 Dec 9;402(6762):689-92
references.pmid: 10604478
references.citation: Curr Biol. 1998 Nov 5;8(22):1211-4
references.pmid: 9811607
references.citation: Proc Natl Acad Sci U S A. 1985 Jun;82(11):3785-9
references.pmid: 3889915
references.citation: Curr Genet. 2006 Sep;50(3):161-71
references.pmid: 16832579
references.citation: Adv Cancer Res. 1990;54:79-139
references.pmid: 2153328
references.citation: J Biochem. 2006 Apr;139(4):741-51
references.pmid: 16672275
references.citation: J Biol Chem. 2005 Jan 28;280(4):2529-35
references.pmid: 15545276
references.citation: EMBO J. 1998 Jul 1;17(13):3556-64
references.pmid: 9649426
references.citation: Mol Microbiol. 1999 May;32(4):671-80
references.pmid: 10361272
references.citation: EMBO J. 1996 May 1;15(9):2227-35
references.pmid: 8641288
references.citation: Mol Cell Biol. 1993 Jul;13(7):3872-81
references.pmid: 8321194
references.citation: Oncogene. 2006 Oct 16;25(48):6361-72
references.pmid: 17041622
references.citation: Cell Metab. 2008 Jul;8(1):38-48
references.pmid: 18590691
references.citation: Mol Microbiol. 2002 Jul;45(1):233-41
references.pmid: 12100562
references.citation: EMBO J. 1992 Jan;11(1):87-96
references.pmid: 1310938
references.citation: Mol Biol Cell. 1996 Jan;7(1):25-42
references.pmid: 8741837
references.citation: Mol Cell Biol. 1999 Jun;19(6):3969-76
references.pmid: 10330137
references.citation: J Bacteriol. 1998 Mar;180(5):1044-52
references.pmid: 9495741
references.citation: Genetics. 2001 Dec;159(4):1435-48
references.pmid: 11779787
references.citation: J Biol Chem. 2002 Nov 8;277(45):43495-504
references.pmid: 12171921
references.citation: Mol Cell Biol. 2003 Jan;23(2):629-35
references.pmid: 12509460
references.citation: Genes Dev. 1999 Dec 15;13(24):3271-9
references.pmid: 10617575
references.citation: Microbiol Mol Biol Rev. 2005 Jun;69(2):262-91
references.pmid: 15944456
references.citation: Mol Biol Cell. 1994 Jan;5(1):105-18
references.pmid: 8186460
references.citation: Proc Natl Acad Sci U S A. 2004 Oct 5;101(40):14315-22
references.pmid: 15353587
references.citation: J Biol Chem. 2005 Mar 11;280(10):9149-59
references.pmid: 15637049
references.citation: J Biol Chem. 1994 Nov 11;269(45):27907-13
references.pmid: 7961723
references.citation: Yeast. 1999 Oct;15(14):1541-53
references.pmid: 10514571
references.citation: J Biol Chem. 2002 Sep 6;277(36):33468-76
references.pmid: 12080055
references.citation: Genes Dev. 2006 Jan 15;20(2):174-84
references.pmid: 16418483
references.citation: Proc Natl Acad Sci U S A. 2002 May 14;99(10):6784-9
references.pmid: 11997479
references.citation: Microbiol Mol Biol Rev. 2005 Mar;69(1):79-100
references.pmid: 15755954
references.citation: J Biol Chem. 2001 Jan 5;276(1):244-50
references.pmid: 11031268
references.citation: Mol Cell. 2003 Jun;11(6):1467-78
references.pmid: 12820961
references.citation: Mol Cell. 2008 Mar 14;29(5):533-5
references.pmid: 18342598
references.citation: Trends Cell Biol. 2006 Apr;16(4):206-12
references.pmid: 16516475
references.citation: Mol Cell Biol. 1992 Jan;12(1):172-82
references.pmid: 1729597
references.citation: Cell. 2004 Dec 29;119(7):969-79
references.pmid: 15620355
references.citation: Cell. 2006 Feb 10;124(3):471-84
references.pmid: 16469695
references.citation: J Cell Biol. 1999 Oct 4;147(1):163-74
references.pmid: 10508863