(Fold Change) acetate biosynthesis ALD6 acetaldehyde dehydrogenase 3.0 acetyl-coa biosynthesis ACS2 acetyl-coa synthetase 2.5

Transcription

1 Supplementary Table 1 Overexpression strains that showed resistance or hypersensitivity to rapamycin. Strains that were more than two-fold enriched on average (and at least 1.8-fold enriched in both experiment replicates) or that were more than two-fold depleted on average (and at least 1.8-fold depleted in both replicates) after rapamycin treatment are listed according to functional category with a brief description ( A single asterisk (*) indicates that the gene was also implicated in the TOR pathway in a global screen of yeast gene-deletion strains (Chan, T.F., Carvalho, J., Riles, L. & Zheng, X.F. A chemical genomics approach toward understanding the global functions of the target of rapamycin protein (TOR). Proc Natl Acad Sci U S A 97, (2000); Xie, M.W. et al. Insights into TOR function and rapamycin response: chemical genomic profiling by using a high-density cell array method. Proc Natl Acad Sci U S A 102, (2005); Parsons, A.B. et al. Integration of chemical-genetic and genetic interaction data links bioactive compounds to cellular target pathways. Nat Biotechnol 22, 62-9 (2004)). A number of other genes in the table have been implicated in the TOR pathway through other methods. A double asterisk (**) indicates that the gene was similarly enriched or depleted after treatment with 100 nm cycloheximide for 20 generations (data available upon request). Cellular Process Gene Name Function Rapamycin (Fold Change) acetate biosynthesis ALD6 acetaldehyde dehydrogenase 3.0 acetyl-coa biosynthesis ACS2 acetyl-coa synthetase 2.5 amino acid metabolism autophagy bud site selection cell cycle cell wall biosynthesis/organization chromatin regulation CPA1 arginine biosynthesis 3.3 ASP3-3 asparaginase expressed during nitrogen starvation 2.5 BAT1 branched-chain amino acid aminotransferase 2.4 YFL030W glycine biosynthesis 3.2 MET31 transcription factor -2.2 ATG19 delivers proteins to preautophagosomal structure 5.3 ATG18** phosphatidylinositol 3,5-bisphosphate-binding protein -3.6 CCZ1* protein involved in vacuolar assembly -2.5 BUD27 protein involved in bud selection and TOR transcriptional regulation -4.9 BUD8 protein of unknown function -6.4 GIC2 protein of unknown function -4.5 CDC16 anaphase-promoting complex subunit -2.3 PCL9 cyclin (Pho85p) -4.0 CDC5 G2/M protein kinase 3.4 CDC123 protein involved in nutritional control of the cell cycle 3.1 WHI4 RNA binding protein that regulates cell size 3.4 SCW4 cell wall protein 2.4 CWH41 ER glucosidase I -2.7 SDP1 negatively regulates Slt2p MAP kinase 3.4 LRG1 putative GTPase-activating protein -2.2 HLR1 regulates cell wall composition in response to osmotic stress 7.0 CBF1 centromere-binding protein 2.3 BRE1* E3 ubiquitin ligase for Rad6p 4.4 HPA2 histone acetyltransferase complex subunit -2.1 RSC4 member of RSC complex 2.1 ZDS2 multicopy suppressor of sin YNL136W NuA4 histone acetyltransferase complex subunit -2.2 SIR3 silencing protein

2 DNA repair DNA replication HFI1* transcriptional coactivator -5.2 APN2 exonuclease 2.1 MSH2 protein involved in mismatch repair 2.9 MMS21 SMO ligase 2.1 SLX4 involved in response to stalled/converging replication forks 6.2 CDC54 MCM initiator complex 4.5 ELG1 protein required for S phase progression and telomere homeostasis -2.4 fatty acid metabolism OLE1 fatty acid desaturase -3.2 gluconeogenesis glucose repression FBP1 fructose-1,6-bisphosphatase 2.1 FYV10 involved in inactivation of fructose-1,6-bisphosphatase 2.5 GSF2 ER integral membrane protein -2.1 transcription factor involved in invasive growth and glucose NRG1 repression -2.3 glutathione biosynthesis GSH1 gamma-glutamylcysteine synthetase -5.7 glycogen metabolism GSY2 glycogen synthase 2.4 PPG1 protein phosphatase, interacts with Tap42p 7.2 glycolysis GCR2 transcriptional activator -4.0 ion transport/homeostasis maltose metabolism mating/mating-type regulation meiosis FET4 iron transporter -5.1 ALR1 magnesium transporter -2.7 ATX2 manganese-trafficking protein -2.0 COS3 Nha1p-binding protein -2.0 PMA1 plasma membrane H + -ATPase -2.2 BSD2* protein that regulates heavy metal ion homeostasis 4.6 HOL1 putative ion transporter -4.5 ZRC1 zinc transporter -3.8 MAL32 alpha-glucosidase 2.3 MAL12 alpha-glucosidase 3.0 STE3 a-factor receptor -2.9 FUS3 MAPK -3.2 ASH1 transcriptional repressor -3.0 MCK1 protein kinase 2.3 MEK1 protein kinase 2.1 RIM11 protein kinase 2.9 CSM3 protein required for chromosome segregation -3.3 RIM101* transcription factor 2.4 mitochondrial genome maintenance HMI1 mitochondrial DNA helicase -2.3 mitochondrial inheritance YPT11 rab-type small GTPase involved in mitochondrial inheritance -3.1 mitosis mrna decay mrna processing/export RTT101 Cullin subunit of E3 ubiquitin ligase complex -3.3 KEL2 protein that negatively regulates mitotic exit -4.4 DCR2 putative phosphoesterase -5.9 SKI2 putative RNA helicase -2.4 NAM7 RNA helicase 6.4 component of the nonsense-mediated mrna decay (NMD) UPF3 pathway -4.5 HMT1 arginine methyltransferase 3.4 YKL059C cleavage and polyadenylation factor subunit -2.3 SGN1 cytoplasmic RNA-binding protein -2.1 GBP2 poly(a+) RNA-binding protein -2.8 PML39 protein required for nuclear retention of unspliced pre-mrnas -2.8 SNP1 required for mrna splicing via spliceosome 2.8 2

3 multidrug resistance SNU71 required for mrna splicing via spliceosome 2.7 AIR2 RING finger protein that interacts with Hmt1p 2.7 PDR16 phosphatidylinositol transfer protein 13.7 PDR17 phosphatidylinositol transfer protein 2.9 PDR3** transcription factor 14.4 YRM1 transcription factor 10.4 NAD + biosynthesis QNS1 NAD + synthetase 2.2 nitrogen compound metabolism PPH3* protein phosphatase involved in the activation of Gln3p 3.8 oxidative stress response YAP1 transcription factor 5.4 peroxisome biogenesis PEX7 import receptor -2.8 phospholipid metabolism/catabolism protein degradation CHO2 phosphatidylethanolamine methyltransferase -3.1 PLB2 phospholipase B 3.4 INO2 transcription factor -2.0 VID22 protein involved in vacuolar protein catabolism 2.3 SUE1 protein required for degradation of unstable cytochrome c -2.0 protein deubiquitination BRE5 ubiquitin protease cofactor 6.9 protein folding protein glycosylation protein sorting/trafficking protein synthesis purine/pyrimidine biosynthesis ribosome biogenesis rrna processing signaling HSP104 heat shock protein 6.3 SSE1 HSP70 family member 11.4 SSE2 HSP70 family member 5.9 YDJ1* HSP70-associated chaperone 3.5 ERO1 protein involved in protein disulfide bond formation in the ER -2.3 KTR6 probable mannosylphosphate transferase -3.1 ALG5 UDP-glucose:dolichyl-phosphate glucosyltransferase -4.0 SAM50 protein import into mitochondrial outer membrane -2.2 TUL1 ubiquitin ligase -3.7 SSH1 protein translocation complex subunit 2.3 SRP72 signal recognition particle subunit 3.4 RPL7B large ribosomal subunit protein -2.1 TIF1* translation initiation factor eif4a 3.2 TIF2 translation initiation factor eif4a 2.6 CDC33 translation initiation factor eif4e 2.0 WRS1 trna synthetase, tryptophan 2.8 GRS1 trna synthetase, glycyl 4.2 GUS1 trna synthetase, glutamyl 2.2 URA5* orotate phosphoribosyltransferase 2.2 PRS3 ribose-phosphate pyrophosphokinase NOG1 putative GTPase required for ribosome biogenesis 2.9 SQT1 protein involved in ribosomal large subunit assembly 2.8 SAS10 component of the ribosomal small subunit processosome 2.3 PNO1 nucleolar protein required for rrna processing 2.2 UTP18 possibly involved in rrna processing 2.4 protein involved in rrna processing and ribosomal large subunit NOP7 biogenesis 2.4 HCA4 RNA helicase 2.9 BMH1* protein involved in rapamycin-sensitive signaling 6.5 PDE1 camp phosphodiesterase -4.1 BAG7 GTPase activating protein -2.9 TOR1* phosphatidylinositol 3-kinase-related kinase 8.4 PIB2* phosphatidylinositol 3-phosphate-binding protein

4 sporulation sterol metabolism TIP41* protein that interacts physically and genetically with Tap42p 2.4 CDC42 small rho-like GTPase involved in polarized growth -2.0 SHO1 transmembrane osmosensor -4.4 protein phosphatase that inactivates MAPK activity during PTC3 osmolarity sensing -2.6 SUR7 integral membrane protein -2.2 NEM1* nuclear envelope protein 2.2 SMA2 protein of unknown function -5.9 ERG13** 3-hydroxy-3-methylglutaryl CoA synthase 2.5 HES1 protein involved in ergosterol biosynthesis -3.1 ARV1* regulator of intracellular sterol distribution -2.5 SUT2 transcription factor -3.8 stress response MSN4 transcription factor -2.5 sulfite metabolism FZF1 transcription factor -2.8 TCA cycle CIT1 citrate synthase 2.1 IDH2* isocitrate dehydrogenase 2.1 MDH2 malate dehydrogenase 3.9 YJL045W similar to Sdh1p -2.3 telomere maintenance STM1 binds to guanine-rich quadruplex nucleic acids 5.7 thiamine metabolism transcription transport transposition trna processing/export vesicular transport THI21 hydroxymethylpyrimidine phosphate kinase 2.2 THI20 thiamine biosynthesis 2.1 YAP3 basic leucine zipper transcription factor 3.1 LEO1 Paf1 complex component 2.2 HPC2 protein required for histone gene transcription -4.0 ELP2* RNA polymerase II Elongator subunit -8.1 ELP4 RNA polymerase II Elongator subunit 4.4 RPB3 RNA polymerase II subunit 2.6 RPB2 RNA polymerase II subunit -3.1 PZF1 transcription factor IIIA 2.1 FEN2 H + -pantothenate symporter -3.9 AZR1 major facilitator superfamily member -3.1 ITR2 myo-inositol permease -3.3 TPO4 polyamine transporter -5.8 YKL174C polyamine transporter -5.6 PUT4 proline and gamma-aminobutyrate permease -3.1 RTT106 regulator of Ty1 transposition 8.3 RTT109 regulator of Ty1 transposition 3.6 LHP1 RNA binding protein 3.3 NCL1* trna (cytosine-5-)-methyltransferase 7.4 UTP8 nucleolar protein required for export of trnas from the nucleus 2.6 APL4 AP-1 complex subunit -2.7 VTI1 Cis-Golgi v-snare -2.8 RET2 coatomer complex subunit -2.3 SEC21 coatomer complex subunit -2.7 MSB3 GTPase-activating protein for Rab GTPases -2.0 VPS60 involved in pseudohyphal growth -2.6 peripheral membrane protein required for Golgi-to-ER retrograde DSL1 traffic 2.4 SEC14 phosphatidylinositol/phosphatidylcholine transfer protein 4.1 VPS29* protein involved in endosome-to-golgi retrograde transport 2.0 SEC24 protein involved in ER to Golgi transport and autophagy 5.3 4

5 unknown function IMH1 protein involved in transport between endosome and Golgi -2.1 YIP1 protein involved in ER to Golgi transport 2.1 APM2 protein of unknown function -2.4 TLG2* trans-golgi network t-snare -4.4 SNC1 v-snare involved in Golgi to plasma membrane transport -2.2 YPR153W deletion mutant shows accumulation of glycogen 2.1 YEL070W deletion suppressor of mpt5 mutation 3.0 DDP1 diadenosine polyphosphate hydrolase 2.5 GIP3 Glc7p-interacting protein -2.3 HSD1 integral ER membrane protein -4.5 PRM6 membrane protein regulated by pheromone -4.4 GUF1* mitochondrial GTPase of unknown function -3.1 YOR205C mitochondrial protein -3.2 CAJ1 nuclear type II J heat shock protein -5.6 GPM3 phosphoglycerate mutase homolog 2.5 FSP2 protein expressed during nitrogen limitation 9.8 IML2 protein involved in plasmid maintenance 24.4 PPT1 protein phosphatase -3.2 PTC4 protein phosphatase type 2C -4.0 YOR129C protein possibly involved in multidrug resistance 4.9 protein regulated by Msn2p, Msn4p, and the Ras-cAMP-cAPK DCS2 signaling pathway 2.2 GIS4 protein that is possibly involved in the RAS/cAMP signaling pathway -7.2 YLR346C protein that is transcriptionally regulated by Pdr1p 2.7 ORM2 protein that may function in protein folding -4.2 FRE7 putative ferric reductase -2.9 FRE5 putative ferric reductase -8.1 SET4 SET domain-containing protein -2.2 YGR287C** similar to alpha-d-glucosidase 7.0 YOL157C similar to alpha-d-glucosidase 7.1 YKL091C similar to Sec14p 5.7 BIT61 subunit of TORC2, binding partner of Tor2p -3.1 transcription is activated by Yrm1p and Yrr1p along with genes YMR102C involved in multidrug resistance 14.5 EFR3-3.1 LIN1 2.5 RBD2-2.8 RBS1-3.3 REH1-2.2 SDS SOR2 2.2 VIP1* -2.3 YBL060W -3.3 YBR284W* -3.2 YCL036W -2.1 YCL049C 2.1 YCR007C -2.2 YDL025C 2.5 YDL063C 2.5 YDL186W -3.3 YDL199C

6 YDR222W 5.0 YDR514C -3.1 YFL054C -2.5 YFR044C 4.7 YGR017W 3.8 YGR018C 2.1 YGR149W 2.8 YGR250C -2.6 YHL008C -2.7 YJL051W -2.5 YKR075C -2.5 YLR152C -2.1 YLR224W -2.9 YLR243W -3.9 YLR297W 3.6 YLR392C -3.3 YML037C -3.4 YMR034C -4.4 YMR210W 4.1 YNL058C -2.1 YNL115C -2.4 YNL305C -2.5 YNR021W 2.1 YOL022C 2.6 YOL125W 2.9 YOR042W 2.7 YOR051C 2.3 YOR052C 2.1 YOR152C 2.3 YOR220W 3.2 YOR228C -2.0 YOR378W -2.8 YPL141C -2.3 YPL158C 3.4 YPL207W -2.9 YPL257W -3.1 YPL260W -2.0 YPL264C -3.2 YPR078C -2.2 YPR115W