title: Cth2 Protein Mediates Early Adaptation of Yeast Cells to Oxidative Stress Conditions.
abstract: Cth2 is an mRNA-binding protein that participates in remodeling yeast cell metabolism in iron starvation conditions by promoting decay of the targeted molecules, in order to avoid excess iron consumption. This study shows that in the absence of Cth2 immediate upregulation of expression of several of the iron regulon genes (involved in high affinity iron uptake and intracellular iron redistribution) upon oxidative stress by hydroperoxide is more intense than in wild type conditions where Cth2 is present. The oxidative stress provokes a temporary increase in the levels of Cth2 (itself a member of the iron regulon). In such conditions Cth2 molecules accumulate at P bodies-like structures when the constitutive mRNA decay machinery is compromised. In addition, a null Δcth2 mutant shows defects, in comparison to CTH2 wild type cells, in exit from α factor-induced arrest at the G1 stage of the cell cycle when hydroperoxide treatment is applied. The cell cycle defects are rescued in conditions that compromise uptake of external iron into the cytosol. The observations support a role of Cth2 in modulating expression of diverse iron regulon genes, excluding those specifically involved in the reductive branch of the high-affinity transport. This would result in immediate adaptation of the yeast cells to an oxidative stress, by controlling uptake of oxidant-promoting iron cations.
authors.affiliation: Departament de Ciències Mèdiques Bàsiques, Universitat de Lleida, IRBLleida,Lleida, Spain.
authors.forename: Laia
authors.initials: L
authors.lastname: Castells-Roca
authors.affiliation: Departament de Ciències Mèdiques Bàsiques, Universitat de Lleida, IRBLleida,Lleida, Spain.
authors.forename: Jordi
authors.initials: J
authors.lastname: Pijuan
authors.affiliation: Departament de Ciències Mèdiques Bàsiques, Universitat de Lleida, IRBLleida,Lleida, Spain.
authors.forename: Francisco
authors.initials: F
authors.lastname: Ferrezuelo
authors.affiliation: Departament de Ciències Mèdiques Bàsiques, Universitat de Lleida, IRBLleida,Lleida, Spain.
authors.forename: Gemma
authors.initials: G
authors.lastname: Bellí
authors.affiliation: Departament de Ciències Mèdiques Bàsiques, Universitat de Lleida, IRBLleida,Lleida, Spain.
authors.forename: Enrique
authors.initials: E
authors.lastname: Herrero
mesh_terms: D000222:Adaptation, Physiological / Q000235:genetics*; D059585:G1 Phase Cell Cycle Checkpoints / Q000187:drug effects / Q000235:genetics; D020869:Gene Expression Profiling; D015966:Gene Expression Regulation, Fungal; D006861:Hydrogen Peroxide / Q000494:pharmacology; D017136:Ion Transport / Q000187:drug effects; D007501:Iron / Q000378:metabolism*; D000072235:Mating Factor; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D010455:Peptides / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics* / Q000378:metabolism; D018085:Regulon / Q000187:drug effects; D012441:Saccharomyces cerevisiae / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction; D013997:Time Factors; D051816:Tristetraprolin / Q000235:genetics* / Q000378:metabolism
chemical_list: D010455:Peptides; D012333:RNA, Messenger; D029701:Saccharomyces cerevisiae Proteins; C091790:TIS11 protein, S cerevisiae; D051816:Tristetraprolin; D000072235:Mating Factor; D006861:Hydrogen Peroxide; D007501:Iron
references.citation: Anal Biochem. 2006 Apr 1;351(1):149-51
references.pmid: 16403430
references.citation: Cell. 2005 Jan 14;120(1):99-110
references.pmid: 15652485
references.citation: Biochem J. 2006 Sep 1;398(2):187-96
references.pmid: 16709151
references.citation: Microbiology. 2006 Dec;152(Pt 12):3595-605
references.pmid: 17159212
references.citation: Eukaryot Cell. 2008 Jan;7(1):20-7
references.pmid: 17993568
references.citation: Mol Cell Biol. 2008 Feb;28(4):1326-37
references.pmid: 18070921
references.citation: Cell Metab. 2008 Jun;7(6):555-64
references.pmid: 18522836
references.citation: J Biol Chem. 2008 Jun 27;283(26):17908-18
references.pmid: 18424442
references.citation: J Biol Chem. 2008 Oct 17;283(42):28527-35
references.pmid: 18715869
references.citation: Mol Syst Biol. 2008;4:223
references.pmid: 18854817
references.citation: Cell Cycle. 2009 Jan 15;8(2):239-52
references.pmid: 19158491
references.citation: RNA. 2009 Jun;15(6):1110-20
references.pmid: 19369426
references.citation: Chem Rev. 2009 Oct;109(10):4536-52
references.pmid: 19705827
references.citation: J Biol Chem. 2011 Jan 21;286(3):2205-14
references.pmid: 21081499
references.citation: PLoS One. 2011;6(2):e17272
references.pmid: 21364882
references.citation: Mol Microbiol. 2011 Jul;81(1):232-48
references.pmid: 21542867
references.citation: Trends Biochem Sci. 2011 Oct;36(10):524-31
references.pmid: 21840721
references.citation: Mol Cell. 2011 Dec 9;44(5):759-69
references.pmid: 22152479
references.citation: PLoS One. 2012;7(5):e37434
references.pmid: 22616008
references.citation: Biochemistry. 2013 Jan 8;52(1):105-14
references.pmid: 23253189
references.citation: Genetics. 2013 Mar;193(3):677-713
references.pmid: 23463800
references.citation: Biochim Biophys Acta. 2013 May;1833(5):997-1005
references.pmid: 23295455
references.citation: Mol Cell Biol. 2013 Jun;33(11):2178-87
references.pmid: 23530061
references.citation: J Mol Biol. 2013 Oct 23;425(20):3750-75
references.pmid: 23467123
references.citation: Biochim Biophys Acta. 2013 Dec;1833(12):3326-37
references.pmid: 24100161
references.citation: Curr Opin Microbiol. 2013 Dec;16(6):662-8
references.pmid: 23962819
references.citation: Microbiology. 2001 Feb;147(Pt 2):289-98
references.pmid: 11158346
references.citation: Mol Microbiol. 2001 Jun;40(5):1067-83
references.pmid: 11401713
references.citation: Mol Biol Cell. 2001 Jun;12(6):1801-10
references.pmid: 11408586
references.citation: J Biol Chem. 2001 Aug 3;276(31):29515-9
references.pmid: 11390404
references.citation: J Biol Chem. 2001 Dec 28;276(52):49244-50
references.pmid: 11673473
references.citation: J Mol Biol. 2002 Apr 26;318(2):251-60
references.pmid: 12051835
references.citation: Methods Enzymol. 2002;350:3-41
references.pmid: 12073320
references.citation: J Biol Chem. 2002 Sep 13;277(37):33749-57
references.pmid: 12095998
references.citation: Bioinformatics. 2004 Jun 12;20(9):1453-4
references.pmid: 14871861
references.citation: Mol Cell. 2004 Jul 23;15(2):303-13
references.pmid: 15260981
references.citation: J Biol Chem. 1996 Oct 4;271(40):24885-93
references.pmid: 8798765
references.citation: J Biol Chem. 1997 May 2;272(18):11770-7
references.pmid: 9115232
references.citation: Nucleic Acids Res. 1998 Feb 15;26(4):942-7
references.pmid: 9461451
references.citation: J Biol Chem. 1998 Mar 27;273(13):7628-36
references.pmid: 9516467
references.citation: Yeast. 1998 Sep 15;14(12):1127-38
references.pmid: 9778798
references.citation: J Biol Chem. 1999 Feb 19;274(8):4537-44
references.pmid: 9988687
references.citation: Mol Microbiol. 1999 May;32(4):753-64
references.pmid: 10361279
references.citation: Nucleic Acids Res. 2006 Jul 1;34(Web Server issue):W498-503
references.pmid: 16845058