title: Nutrient sensing kinases PKA and Sch9 phosphorylate the catalytic domain of the ubiquitin-conjugating enzyme Cdc34.
abstract: Cell division is controlled in part by the timely activation of the CDK, Cdc28, through its association with G1 and G2 cyclins. Cdc28 complexes are regulated in turn by the ubiquitin conjugating enzyme Cdc34 and SCF ubiquitin ligase complexes of the ubiquitin-proteasome system (UPS) to control the initiation of DNA replication. Here we demonstrate that the nutrient sensing kinases PKA and Sch9 phosphorylate S97 of Cdc34. S97 is conserved across species and restricted to the catalytic domain of Cdc34/Ubc7-like E2s. Cdc34-S97 phosphorylation is cell cycle regulated, elevated during active cell growth and division and decreased during cell cycle arrest. Cell growth and cell division are orchestrated to maintain cell size homeostasis over a wide range of nutrient conditions. Cells monitor changes in their environment through nutrient sensing protein kinases. Thus Cdc34 phosphorylation by PKA and Sch9 provides a direct tether between G1 cell division events and cell growth.
authors.affiliation: Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, Indiana, United States of America.
authors.forename: Ross
authors.initials: R
authors.lastname: Cocklin
authors.forename: Mark
authors.initials: M
authors.lastname: Goebl
mesh_terms: D064173:Anaphase-Promoting Complex-Cyclosome; D000818:Animals; D020134:Catalytic Domain; D002453:Cell Cycle / Q000502:physiology; D002455:Cell Division; D048429:Cell Size; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism*; D005502:Food; D006801:Humans; D010766:Phosphorylation; D011494:Protein Kinases / Q000378:metabolism*; D013045:Species Specificity; D044763:Ubiquitin-Conjugating Enzymes; D043743:Ubiquitin-Protein Ligase Complexes / Q000737:chemistry / Q000378:metabolism*
chemical_list: C577447:CDC34 protein, human; D044763:Ubiquitin-Conjugating Enzymes; D043743:Ubiquitin-Protein Ligase Complexes; D064173:Anaphase-Promoting Complex-Cyclosome; D011494:Protein Kinases; C071569:SCH9 protein kinase; D017868:Cyclic AMP-Dependent Protein Kinases
references.citation: Science. 1999 Nov 5;286(5442):1153-5
references.pmid: 10550052
references.citation: Nature. 1996 Nov 7;384(6604):33
references.pmid: 8900272
references.citation: Anal Biochem. 1976 May 7;72:248-54
references.pmid: 942051
references.citation: Cell Mol Life Sci. 2002 Jun;59(6):903-8
references.pmid: 12169020
references.citation: Yeast. 1994 Oct;10(10):1305-10
references.pmid: 7900419
references.citation: J Biol Chem. 2003 Jun 27;278(26):23460-71
references.pmid: 12704202
references.citation: Mol Cell. 2005 Nov 23;20(4):589-99
references.pmid: 16307922
references.citation: Microbiol Mol Biol Rev. 2003 Sep;67(3):376-99, table of contents
references.pmid: 12966141
references.citation: J Biol Chem. 1980 Mar 10;255(5):2137-45
references.pmid: 6243658
references.citation: J Biol Chem. 2005 Sep 23;280(38):33076-82
references.pmid: 16049009
references.citation: PLoS One. 2007 Aug 15;2(8):e748
references.pmid: 17710147
references.citation: Mol Cell Biol. 1987 Apr;7(4):1371-7
references.pmid: 3037314
references.citation: Genetics. 2009 Oct;183(2):413-22, 1SI-13SI
references.pmid: 19652178
references.citation: Science. 1990 Aug 24;249(4971):908-12
references.pmid: 2392681
references.citation: Biochem J. 2008 Feb 15;410(1):1-17
references.pmid: 18215151
references.citation: Biochemistry. 1995 Aug 22;34(33):10569-77
references.pmid: 7654713
references.citation: Science. 1988 Sep 9;241(4871):1331-5
references.pmid: 2842867
references.citation: Biochem Biophys Res Commun. 2007 Aug 10;359(4):921-7
references.pmid: 17574209
references.citation: J Biol Chem. 1998 Feb 13;273(7):4040-5
references.pmid: 9461595
references.citation: Genes Dev. 1988 May;2(5):517-27
references.pmid: 3290050
references.citation: Mech Ageing Dev. 2002 May;123(9):1229-44
references.pmid: 12020945
references.citation: Genetics. 2000 Apr;154(4):1509-21
references.pmid: 10747049
references.citation: Microbiol Mol Biol Rev. 2006 Mar;70(1):253-82
references.pmid: 16524925
references.citation: Mol Cell Biol. 1990 Sep;10(9):4518-23
references.pmid: 2201893
references.citation: Curr Biol. 1996 Nov 1;6(11):1426-34
references.pmid: 8939604
references.citation: Mech Ageing Dev. 2002 Jan;123(2-3):121-30
references.pmid: 11718806
references.citation: Cell. 2011 Sep 16;146(6):969-79
references.pmid: 21906795
references.citation: Genetics. 2011 Mar;187(3):701-15
references.pmid: 21196523
references.citation: Curr Biol. 2004 Sep 21;14(18):R787-96
references.pmid: 15380093
references.citation: Nature. 1993 Dec 2;366(6454):461-4
references.pmid: 8247153
references.citation: Prog Biophys Mol Biol. 1999;71(3-4):313-41
references.pmid: 10354702
references.citation: Mol Cell. 2007 Jun 8;26(5):663-74
references.pmid: 17560372
references.citation: Cell. 2009 Feb 20;136(4):731-45
references.pmid: 19239892
references.citation: Biochem J. 2007 Aug 1;405(3):569-81
references.pmid: 17461777
references.citation: Science. 2001 Apr 6;292(5514):107-10
references.pmid: 11292875
references.citation: Curr Opin Struct Biol. 2011 Apr;21(2):257-64
references.pmid: 21288713
references.citation: Annu Rev Cell Dev Biol. 2008;24:475-99
references.pmid: 18598214
references.citation: Cell. 1997 Oct 17;91(2):209-19
references.pmid: 9346238
references.citation: Genes Dev. 1997 Nov 15;11(22):3046-60
references.pmid: 9367986
references.citation: Proc Natl Acad Sci U S A. 2005 Oct 4;102(40):14238-43
references.pmid: 16176982
references.citation: Mol Biol Cell. 2007 Oct;18(10):4180-9
references.pmid: 17699586
references.citation: Cell. 1990 Nov 30;63(5):999-1011
references.pmid: 2147873
references.citation: Physiol Rev. 2002 Apr;82(2):373-428
references.pmid: 11917093
references.citation: Science. 1999 Apr 23;284(5414):662-5
references.pmid: 10213692
references.citation: Cell Div. 2011 Mar 31;6:7
references.pmid: 21453497
references.citation: Curr Biol. 1994 Nov 1;4(11):973-82
references.pmid: 7874496
references.citation: Cell. 1988 May 20;53(4):555-66
references.pmid: 2836063
references.citation: Proc Natl Acad Sci U S A. 2005 Oct 18;102(42):15053-8
references.pmid: 16210246
references.citation: Mol Cell Biol. 1994 May;14(5):3022-9
references.pmid: 8164658
references.citation: Cell Cycle. 2008 May 15;7(10):1391-401
references.pmid: 18418079
references.citation: Mol Microbiol. 2007 Mar;63(5):1482-94
references.pmid: 17302822
references.citation: Eur J Biochem. 1996 Apr 1;237(1):136-42
references.pmid: 8620865
references.citation: J Biol Chem. 2004 Nov 5;279(45):46715-22
references.pmid: 15339905
references.citation: Mol Cell. 2010 Mar 26;37(6):784-96
references.pmid: 20347421
references.citation: Cell. 1987 Jul 17;50(2):277-87
references.pmid: 3036373
references.citation: Science. 2001 Apr 6;292(5514):104-6
references.pmid: 11292874
references.citation: Yeast. 2005 May;22(7):553-64
references.pmid: 15942932
references.citation: Annu Rev Cell Dev Biol. 1999;15:435-67
references.pmid: 10611969
references.citation: Biochem J. 2008 Feb 15;410(1):19-37
references.pmid: 18215152
references.citation: Mol Cell Biol. 1995 Oct;15(10):5635-44
references.pmid: 7565715
references.citation: Science. 1999 Aug 6;285(5429):901-6
references.pmid: 10436161
references.citation: Nat Cell Biol. 2004 Feb;6(2):138-45
references.pmid: 14743219
references.citation: Mol Cell Biol. 1995 Mar;15(3):1210-9
references.pmid: 7862115
references.citation: Mol Cell Biol. 2003 Aug;23(15):5388-400
references.pmid: 12861024
references.citation: Genes Dev. 1994 May 1;8(9):1058-70
references.pmid: 7926787
references.citation: Mol Biol Cell. 1997 Aug;8(8):1427-37
references.pmid: 9285816
references.citation: Cell. 2005 Dec 16;123(6):1107-20
references.pmid: 16360039
references.citation: J Biol Chem. 1991 Sep 25;266(27):17932-5
references.pmid: 1917932