Publications

2023

EGOC inhibits TOROID polymerization by structurally activating TORC1.

Prouteau M, Bourgoint C, Felix J, Bonadei L, Sadian Y, Gabus C, Savvides SN, Gutsche I, Desfosses A, Loewith R

Nat Struct Mol Biol,2023 Jan 26:

DOI: 10.1038/s41594-022-00912-6

Dynamic metabolome profiling uncovers potential TOR signaling genes.

Reichling S, Doubleday PF, Germade T, Bergmann A, Loewith R, Sauer U, Holbrook-Smith D

Elife,2023 Jan 412:

DOI: 10.7554/eLife.84295

2022

Ultrastructure expansion microscopy reveals the cellular architecture of budding and fission yeast.

Hinterndorfer K, Laporte MH, Mikus F, Tafur L, Bourgoint C, Prouteau M, Dey G, Loewith R, Guichard P, Hamel V

J Cell Sci,2022 Dec 15135(24):

DOI: 10.1242/jcs.260240

Cryo-EM structure of the SEA complex.

Tafur L, Hinterndorfer K, Gabus C, Lamanna C, Bergmann A, Sadian Y, Hamdi F, Kyrilis FL, Kastritis PL, Loewith R

Nature,2022 Nov611(7935):

DOI: 10.1038/s41586-022-05370-0

2021

Chemical-Biology-derived in vivo Sensors: Past, Present, and Future.

Loewith R, Roux A, Pertz O

Chimia (Aarau),2021 Dec 2275(12):

DOI: 10.2533/chimia.2021.1017

Flipper Probes for the Community.

Assies L, García-Calvo J, Piazzolla F, Sanchez S, Kato T, Reymond L, Goujon A, Colom A, López-Andarias J, Straková K, Mahecic D, Mercier V, Riggi M, Jiménez-Rojo N, Roffay C, Licari G, Tsemperouli M, Neuhaus F, Fürstenberg A, Vauthey E, Hoogendoorn S, Gonzalez-Gaitan M, Zumbuehl A, Sugihara K, Gruenberg J, Riezman H, Loewith R, Manley S, Roux A, Winssinger N, Sakai N, Pitsch S, Matile S

Chimia (Aarau),2021 Dec 2275(12):

DOI: 10.2533/chimia.2021.1004

Passive coupling of membrane tension and cell volume during active response of cells to osmosis.

Roffay C, Molinard G, Kim K, Urbanska M, Andrade V, Barbarasa V, Nowak P, Mercier V, García-Calvo J, Matile S, Loewith R, Echard A, Guck J, Lenz M, Roux A

Proc Natl Acad Sci U S A,2021 Nov 23118(47):

DOI: 10.1073/pnas.2103228118

Identification of a Covalent Importin-5 Inhibitor, Goyazensolide, from a Collective Synthesis of Furanoheliangolides.

Liu W, Patouret R, Barluenga S, Plank M, Loewith R, Winssinger N

ACS Cent Sci,2021 Jun 237(6):

DOI: 10.1021/acscentsci.1c00056

Phosphoproteomic Effects of Acute Depletion of PP2A Regulatory Subunit Cdc55.

Plank M, Berti M, Loewith R

Proteomics,2021 Jan21(1):

DOI: 10.1002/pmic.202000166

2020

Resolving the Communication GAPs Upstream of TORC1.

Puschmann R, Loewith R

Dev Cell,2020 Nov 955(3):

DOI: 10.1016/j.devcel.2020.10.007

TOR complex 2 (TORC2) signaling and the ESCRT machinery cooperate in the protection of plasma membrane integrity in yeast.

Schmidt O, Weyer Y, Sprenger S, Widerin MA, Eising S, Baumann V, Angelova M, Loewith R, Stefan CJ, Hess MW, Fröhlich F, Teis D

J Biol Chem,2020 Aug 21295(34):

DOI: 10.1074/jbc.RA120.013222

Structural Insights into TOR Signaling.

Tafur L, Kefauver J, Loewith R

Genes (Basel),2020 Aug 411(8):

DOI: 10.3390/genes11080885

The flipside of the TOR coin - TORC2 and plasma membrane homeostasis at a glance.

Riggi M, Kusmider B, Loewith R

J Cell Sci,2020 May 11133(9):

DOI: 10.1242/jcs.242040

Chemical Genetics of AGC-kinases Reveals Shared Targets of Ypk1, Protein Kinase A and Sch9.

Plank M, Perepelkina M, Müller M, Vaga S, Zou X, Bourgoint C, Berti M, Saarbach J, Haesendonckx S, Winssinger N, Aebersold R, Loewith R

Mol Cell Proteomics,2020 Apr19(4):

DOI: 10.1074/mcp.RA120.001955

The Aspartic Protease Ddi1 Contributes to DNA-Protein Crosslink Repair in Yeast.

Serbyn N, Noireterre A, Bagdiul I, Plank M, Michel AH, Loewith R, Kornmann B, Stutz F

Mol Cell,2020 Mar 577(5):

DOI: 10.1016/j.molcel.2019.12.007

2019

Tricalbin-Mediated Contact Sites Control ER Curvature to Maintain Plasma Membrane Integrity.

Collado J, Kalemanov M, Campelo F, Bourgoint C, Thomas F, Loewith R, Martínez-Sánchez A, Baumeister W, Stefan CJ, Fernández-Busnadiego R

Dev Cell,2019 Nov 1851(4):

DOI: 10.1016/j.devcel.2019.10.018

TORC2 controls endocytosis through plasma membrane tension.

Riggi M, Bourgoint C, Macchione M, Matile S, Loewith R, Roux A

J Cell Biol,2019 Jul 1218(7):

DOI: 10.1083/jcb.201901096

Sphingolipids and membrane targets for therapeutics.

Loewith R, Riezman H, Winssinger N

Curr Opin Chem Biol,2019 Jun50:

DOI: 10.1016/j.cbpa.2019.02.015

TOR Signaling Is Going through a Phase.

Prouteau M, Loewith R

Cell Metab,2019 May 729(5):

DOI: 10.1016/j.cmet.2019.04.010

2018

Regulation of Cellular Metabolism through Phase Separation of Enzymes.

Prouteau M, Loewith R

Biomolecules,2018 Dec 38(4):

DOI: 10.3390/biom8040160

Decrease in plasma membrane tension triggers PtdIns(4,5)P₂ phase separation to inactivate TORC2.

Riggi M, Niewola-Staszkowska K, Chiaruttini N, Colom A, Kusmider B, Mercier V, Soleimanpour S, Stahl M, Matile S, Roux A, Loewith R

Nat Cell Biol,2018 Sep20(9):

DOI: 10.1038/s41556-018-0150-z

Target of rapamycin complex 2-dependent phosphorylation of the coat protein Pan1 by Akl1 controls endocytosis dynamics in Saccharomyces cerevisiae.

Bourgoint C, Rispal D, Berti M, Filipuzzi I, Helliwell SB, Prouteau M, Loewith R

J Biol Chem,2018 Aug 3293(31):

DOI: 10.1074/jbc.RA117.001615

Systematic analysis of complex genetic interactions.

Kuzmin E, VanderSluis B, Wang W, Tan G, Deshpande R, Chen Y, Usaj M, Balint A, Mattiazzi Usaj M, van Leeuwen J, Koch EN, Pons C, Dagilis AJ, Pryszlak M, Wang JZY, Hanchard J, Riggi M, Xu K, Heydari H, San Luis BJ, Shuteriqi E, Zhu H, Van Dyk N, Sharifpoor S, Costanzo M, Loewith R, Caudy A, Bolnick D, Brown GW, Andrews BJ, Boone C, Myers CL

Science,2018 Apr 20360(6386):

DOI: 10.1126/science.aao1729

2017

Cryo-EM structure of Saccharomyces cerevisiae target of rapamycin complex 2.

Karuppasamy M, Kusmider B, Oliveira TM, Gaubitz C, Prouteau M, Loewith R, Schaffitzel C

Nat Commun,2017 Nov 238(1):

DOI: 10.1038/s41467-017-01862-0

TORC1 organized in inhibited domains (TOROIDs) regulate TORC1 activity.

Prouteau M, Desfosses A, Sieben C, Bourgoint C, Lydia Mozaffari N, Demurtas D, Mitra AK, Guichard P, Manley S, Loewith R

Nature,2017 Oct 12550(7675):

DOI: 10.1038/nature24021

Tensing Up for Lipid Droplet Formation.

Roux A, Loewith R

Dev Cell,2017 Jun 1941(6):

DOI: 10.1016/j.devcel.2017.06.001

A pathway of targeted autophagy is induced by DNA damage in budding yeast.

Eapen VV, Waterman DP, Bernard A, Schiffmann N, Sayas E, Kamber R, Lemos B, Memisoglu G, Ang J, Mazella A, Chuartzman SG, Loewith RJ, Schuldiner M, Denic V, Klionsky DJ, Haber JE

Proc Natl Acad Sci U S A,2017 Feb 14114(7):

DOI: 10.1073/pnas.1614364114

2016

Reciprocal Regulation of Target of Rapamycin Complex 1 and Potassium Accumulation.

Primo C, Ferri-Blázquez A, Loewith R, Yenush L

J Biol Chem,2017 Jan 13292(2):

DOI: 10.1074/jbc.M116.746982

Dual action antifungal small molecule modulates multidrug efflux and TOR signaling.

Shekhar-Guturja T, Gunaherath GM, Wijeratne EM, Lambert JP, Averette AF, Lee SC, Kim T, Bahn YS, Tripodi F, Ammar R, Döhl K, Niewola-Staszkowska K, Schmitt L, Loewith RJ, Roth FP, Sanglard D, Andes D, Nislow C, Coccetti P, Gingras AC, Heitman J, Gunatilaka AA, Cowen LE

Nat Chem Biol,2016 Oct12(10):

DOI: 10.1038/nchembio.2165

TORC2 Structure and Function.

Gaubitz C, Prouteau M, Kusmider B, Loewith R

Trends Biochem Sci,2016 Jun41(6):

DOI: 10.1016/j.tibs.2016.04.001

A Signaling Lipid Associated with Alzheimer's Disease Promotes Mitochondrial Dysfunction.

Kennedy MA, Moffat TC, Gable K, Ganesan S, Niewola-Staszkowska K, Johnston A, Nislow C, Giaever G, Harris LJ, Loewith R, Zaremberg V, Harper ME, Dunn T, Bennett SAL, Baetz K

Sci Rep,2016 Jan 136:

DOI: 10.1038/srep19332

2015

TORC1 and TORC2 work together to regulate ribosomal protein S6 phosphorylation in Saccharomyces cerevisiae.

Yerlikaya S, Meusburger M, Kumari R, Huber A, Anrather D, Costanzo M, Boone C, Ammerer G, Baranov PV, Loewith R

Mol Biol Cell,2016 Jan 1527(2):

DOI: 10.1091/mbc.E15-08-0594

TOR Complexes and the Maintenance of Cellular Homeostasis.

Eltschinger S, Loewith R

Trends Cell Biol,2016 Feb26(2):

DOI: 10.1016/j.tcb.2015.10.003

Molecular Basis of the Rapamycin Insensitivity of Target Of Rapamycin Complex 2.

Gaubitz C, Oliveira TM, Prouteau M, Leitner A, Karuppasamy M, Konstantinidou G, Rispal D, Eltschinger S, Robinson GC, Thore S, Aebersold R, Schaffitzel C, Loewith R

Mol Cell,2015 Jun 1858(6):

DOI: 10.1016/j.molcel.2015.04.031

Target of Rapamycin Complex 2 Regulates Actin Polarization and Endocytosis via Multiple Pathways.

Rispal D, Eltschinger S, Stahl M, Vaga S, Bodenmiller B, Abraham Y, Filipuzzi I, Movva NR, Aebersold R, Helliwell SB, Loewith R

J Biol Chem,2015 Jun 12290(24):

DOI: 10.1074/jbc.M114.627794

2014

Systematic lipidomic analysis of yeast protein kinase and phosphatase mutants reveals novel insights into regulation of lipid homeostasis.

da Silveira Dos Santos AX, Riezman I, Aguilera-Romero MA, David F, Piccolis M, Loewith R, Schaad O, Riezman H

Mol Biol Cell,2014 Oct 1525(20):

DOI: 10.1091/mbc.E14-03-0851

Roles for PI(3,5)P2 in nutrient sensing through TORC1.

Jin N, Mao K, Jin Y, Tevzadze G, Kauffman EJ, Park S, Bridges D, Loewith R, Saltiel AR, Klionsky DJ, Weisman LS

Mol Biol Cell,2014 Apr25(7):

DOI: 10.1091/mbc.E14-01-0021

A neurotoxic glycerophosphocholine impacts PtdIns-4, 5-bisphosphate and TORC2 signaling by altering ceramide biosynthesis in yeast.

Kennedy MA, Gable K, Niewola-Staszkowska K, Abreu S, Johnston A, Harris LJ, Reggiori F, Loewith R, Dunn T, Bennett SA, Baetz K

PLoS Genet,2014 Jan10(1):

DOI: 10.1371/journal.pgen.1004010

2013

TORC2 signaling pathway guarantees genome stability in the face of DNA strand breaks.

Shimada K, Filipuzzi I, Stahl M, Helliwell SB, Studer C, Hoepfner D, Seeber A, Loewith R, Movva NR, Gasser SM

Mol Cell,2013 Sep 2651(6):

DOI: 10.1016/j.molcel.2013.08.019

Growth control: function follows form.

Loewith R

Curr Biol,2013 Jul 2223(14):

DOI: 10.1016/j.cub.2013.05.048

2012

Amino acid signaling in high definition.

Gaubitz C, Loewith R

Structure,2012 Dec 520(12):

DOI: 10.1016/j.str.2012.11.006

Identification of a small molecule yeast TORC1 inhibitor with a multiplex screen based on flow cytometry.

Chen J, Young SM, Allen C, Seeber A, Péli-Gulli MP, Panchaud N, Waller A, Ursu O, Yao T, Golden JE, Strouse JJ, Carter MB, Kang H, Bologa CG, Foutz TD, Edwards BS, Peterson BR, Aubé J, Werner-Washburne M, Loewith RJ, De Virgilio C, Sklar LA

ACS Chem Biol,2012 Apr 207(4):

DOI: 10.1021/cb200452r

Plasma membrane stress induces relocalization of Slm proteins and activation of TORC2 to promote sphingolipid synthesis.

Berchtold D, Piccolis M, Chiaruttini N, Riezman I, Riezman H, Roux A, Walther TC, Loewith R

Nat Cell Biol,2012 Apr 1514(5):

DOI: 10.1038/ncb2480

2011

Target of rapamycin (TOR) in nutrient signaling and growth control.

Loewith R, Hall MN

Genetics,2011 Dec189(4):

DOI: 10.1534/genetics.111.133363

Mitochondrial genomic dysfunction causes dephosphorylation of Sch9 in the yeast Saccharomyces cerevisiae.

Kawai S, Urban J, Piccolis M, Panchaud N, De Virgilio C, Loewith R

Eukaryot Cell,2011 Oct10(10):

DOI: 10.1128/EC.05157-11

Sch9 regulates ribosome biogenesis via Stb3, Dot6 and Tod6 and the histone deacetylase complex RPD3L.

Huber A, French SL, Tekotte H, Yerlikaya S, Stahl M, Perepelkina MP, Tyers M, Rougemont J, Beyer AL, Loewith R

EMBO J,2011 Jul 530(15):

DOI: 10.1038/emboj.2011.221

A brief history of TOR.

Loewith R

Biochem Soc Trans,2011 Apr39(2):

DOI: 10.1042/BST0390437

Chemical biology approaches to membrane homeostasis and function.

Takahashi-Umebayashi M, Pineau L, Hannich T, Zumbuehl A, Doval DA, Matile S, Heinis C, Turcatti G, Loewith R, Roux A, Reymond L, Johnsson K, Riezman H

Chimia (Aarau),201165(11):

DOI: 10.2533/chimia.2011.849

2010

Phosphoproteomic analysis reveals interconnected system-wide responses to perturbations of kinases and phosphatases in yeast.

Bodenmiller B, Wanka S, Kraft C, Urban J, Campbell D, Pedrioli PG, Gerrits B, Picotti P, Lam H, Vitek O, Brusniak MY, Roschitzki B, Zhang C, Shokat KM, Schlapbach R, Colman-Lerner A, Nolan GP, Nesvizhskii AI, Peter M, Loewith R, von Mering C, Aebersold R

Sci Signal,2010 Dec 213(153):

DOI: 10.1126/scisignal.2001182

Profiling a Selective Probe for RTG Branch of Yeast TORC1 Signaling Pathway

Chen J, Young SM, Allen C, Waller A, Ursu O, Strouse JJ, Yao T, Golden JE, Peterson BR, Foutz TD, Chavez SE, Perez D, Evangelisti AM, Garcia MJ, Bologa CG, Carter MB, Salas VM, Oprea TI, Edwards BS, Panchaud N, De Virgilio C, Seeber A, Loewith R, Manzanilla E, Werner-Washburne M, Aubé J, Sklar LA

,2010:

2009

The Vam6 GEF controls TORC1 by activating the EGO complex.

Binda M, Péli-Gulli MP, Bonfils G, Panchaud N, Urban J, Sturgill TW, Loewith R, De Virgilio C

Mol Cell,2009 Sep 1135(5):

DOI: 10.1016/j.molcel.2009.06.033

Characterization of the rapamycin-sensitive phosphoproteome reveals that Sch9 is a central coordinator of protein synthesis.

Huber A, Bodenmiller B, Uotila A, Stahl M, Wanka S, Gerrits B, Aebersold R, Loewith R

Genes Dev,2009 Aug 1523(16):

DOI: 10.1101/gad.532109

Functional interactions between sphingolipids and sterols in biological membranes regulating cell physiology.

Guan XL, Souza CM, Pichler H, Dewhurst G, Schaad O, Kajiwara K, Wakabayashi H, Ivanova T, Castillon GA, Piccolis M, Abe F, Loewith R, Funato K, Wenk MR, Riezman H

Mol Biol Cell,2009 Apr20(7):

DOI: 10.1091/mbc.e08-11-1126

Sfp1 interaction with TORC1 and Mrs6 reveals feedback regulation on TOR signaling.

Lempiäinen H, Uotila A, Urban J, Dohnal I, Ammerer G, Loewith R, Shore D

Mol Cell,2009 Mar 2733(6):

DOI: 10.1016/j.molcel.2009.01.034

Active-site inhibitors of mTOR target rapamycin-resistant outputs of mTORC1 and mTORC2.

Feldman ME, Apsel B, Uotila A, Loewith R, Knight ZA, Ruggero D, Shokat KM

PLoS Biol,2009 Feb 107(2):

DOI: 10.1371/journal.pbio.1000038

Arsenic toxicity to Saccharomyces cerevisiae is a consequence of inhibition of the TORC1 kinase combined with a chronic stress response.

Hosiner D, Lempiäinen H, Reiter W, Urban J, Loewith R, Ammerer G, Schweyen R, Shore D, Schüller C

Mol Biol Cell,2009 Feb20(3):

DOI: 10.1091/mbc.e08-04-0438

2008

Caffeine extends yeast lifespan by targeting TORC1.

Wanke V, Cameroni E, Uotila A, Piccolis M, Urban J, Loewith R, De Virgilio C

Mol Microbiol,2008 Jul69(1):

DOI: 10.1111/j.1365-2958.2008.06292.x

2007

Sch9 is a major target of TORC1 in Saccharomyces cerevisiae.

Urban J, Soulard A, Huber A, Lippman S, Mukhopadhyay D, Deloche O, Wanke V, Anrather D, Ammerer G, Riezman H, Broach JR, De Virgilio C, Hall MN, Loewith R

Mol Cell,2007 Jun 826(5):

DOI: 10.1016/j.molcel.2007.04.020

2006

Mutual antagonism of target of rapamycin and calcineurin signaling.

Mulet JM, Martin DE, Loewith R, Hall MN

J Biol Chem,2006 Nov 3281(44):

DOI: 10.1074/jbc.M604244200

Cell growth control: little eukaryotes make big contributions.

De Virgilio C, Loewith R

Oncogene,2006 Oct 1625(48):

DOI: 10.1038/sj.onc.1209884

A pharmacological map of the PI3-K family defines a role for p110alpha in insulin signaling.

Knight ZA, Gonzalez B, Feldman ME, Zunder ER, Goldenberg DD, Williams O, Loewith R, Stokoe D, Balla A, Toth B, Balla T, Weiss WA, Williams RL, Shokat KM

Cell,2006 May 19125(4):

DOI: 10.1016/j.cell.2006.03.035

TOR signaling in growth and metabolism.

Wullschleger S, Loewith R, Hall MN

Cell,2006 Feb 10124(3):

DOI: 10.1016/j.cell.2006.01.016

The TOR signalling network from yeast to man.

De Virgilio C, Loewith R

Int J Biochem Cell Biol,200638(9):

DOI: 10.1016/j.biocel.2006.02.013

2005

Molecular organization of target of rapamycin complex 2.

Wullschleger S, Loewith R, Oppliger W, Hall MN

J Biol Chem,2005 Sep 2280(35):

DOI: 10.1074/jbc.M505553200

Tor2 directly phosphorylates the AGC kinase Ypk2 to regulate actin polarization.

Kamada Y, Fujioka Y, Suzuki NN, Inagaki F, Wullschleger S, Loewith R, Hall MN, Ohsumi Y

Mol Cell Biol,2005 Aug25(16):

DOI: 10.1128/MCB.25.16.7239-7248.2005

2004

Mammalian TOR complex 2 controls the actin cytoskeleton and is rapamycin insensitive.

Jacinto E, Loewith R, Schmidt A, Lin S, Rüegg MA, Hall A, Hall MN

Nat Cell Biol,2004 Nov6(11):

DOI: 10.1038/ncb1183

Genome-wide lethality screen identifies new PI4,5P2 effectors that regulate the actin cytoskeleton.

Audhya A, Loewith R, Parsons AB, Gao L, Tabuchi M, Zhou H, Boone C, Hall MN, Emr SD

EMBO J,2004 Oct 123(19):

DOI: 10.1038/sj.emboj.7600384

2002

Two TOR complexes, only one of which is rapamycin sensitive, have distinct roles in cell growth control.

Loewith R, Jacinto E, Wullschleger S, Lorberg A, Crespo JL, Bonenfant D, Oppliger W, Jenoe P, Hall MN

Mol Cell,2002 Sep10(3):

DOI: 10.1016/s1097-2765(02)00636-6

Human ING1 proteins differentially regulate histone acetylation.

Vieyra D, Loewith R, Scott M, Bonnefin P, Boisvert FM, Cheema P, Pastyryeva S, Meijer M, Johnston RN, Bazett-Jones DP, McMahon S, Cole MD, Young D, Riabowol K

J Biol Chem,2002 Aug 16277(33):

DOI: 10.1074/jbc.M200197200

2001

Pho23 is associated with the Rpd3 histone deacetylase and is required for its normal function in regulation of gene expression and silencing in Saccharomyces cerevisiae.

Loewith R, Smith JS, Meijer M, Williams TJ, Bachman N, Boeke JD, Young D

J Biol Chem,2001 Jun 29276(26):

DOI: 10.1074/jbc.M102176200

2000

Three yeast proteins related to the human candidate tumor suppressor p33(ING1) are associated with histone acetyltransferase activities.

Loewith R, Meijer M, Lees-Miller SP, Riabowol K, Young D

Mol Cell Biol,2000 Jun20(11):

DOI: 10.1128/mcb.20.11.3807-3816.2000

Skh1, the MEK component of the mkh1 signaling pathway in Schizosaccharomyces pombe.

Loewith R, Hubberstey A, Young D

J Cell Sci,2000 Jan113 ( Pt 1:

1996

Mammalian CAP interacts with CAP, CAP2, and actin.

Hubberstey A, Yu G, Loewith R, Lakusta C, Young D

J Cell Biochem,1996 Jun 161(3):

DOI: 10.1002/(SICI)1097-4644(19960601)61:3%3C459::AID-JCB13%3E3.0.CO;2-E

Robbie Loewith