Table S1. Pathway analysis of up-regulated proteins in MV4-11 cells treated with MLN4924 Pathway identifier Pathway name # Entities found # Entities total Entities ratio Entities PValue REACT_1783 G1/S Transition G2/M DNA replication checkpoint Mitotic G1-G1/S phases S Phase Detoxification of Reactive Oxygen Species G2/M Checkpoints Association of licensing factors with the pre-replicative complex Cell Cycle DNA Replication Synthesis and interconversion of nucleotide di- and triphosphates G1/S-Specific Transcription Cell Cycle, Mitotic Cell Cycle Checkpoints 5 113 0.01130226 3.37E-04 2 7 7.00E-04 6.60E-04 5 5 139 139 0.013902781 0.013902781 8.56E-04 8.56E-04 3 3 52 53 0.00520104 0.00530106 0.002714252 0.002863216 2 9 4 15 579 117 0.0015003 0.057911582 0.01170234 0.002947885 0.00318196 0.003479343 3 57 0.00570114 0.003509128 2 8 17 496 0.00170034 0.049609922 0.003760874 0.00440028 4 128 0.012802561 0.004776118 REACT_1846 REACT_21267 REACT_899 REACT_264249 REACT_828 REACT_1181 REACT_115566 REACT_383 REACT_21330 REACT_683 REACT_152 REACT_1538 REACT_1574 REACT_1006 REACT_207 REACT_829 REACT_1857 REACT_471 REACT_120956 REACT_2014 REACT_264071 REACT_264075 REACT_2198 REACT_1698 REACT_405 REACT_2174 Cyclin E associated events during G1/S transition Polo-like kinase mediated events Removal of licensing factors from origins Regulation of DNA replication Cyclin A/B1 associated events during G2/M transition E2F mediated regulation of DNA replication Cellular responses to stress Synthesis of DNA HSF1 activation Attenuation phase Translesion synthesis by Y family DNA polymerases bypasses lesions on DNA template Metabolism of nucleotides Transport of the SLBP Dependant Mature mRNA DNA Damage Bypass 3 69 0.00690138 0.005953821 2 23 0.00230046 0.006746026 3 74 0.00740148 0.007209485 3 77 0.00770154 0.008032697 2 26 0.00260052 0.008533888 2 33 0.00330066 0.013427605 6 3 2 2 374 108 43 46 0.037407481 0.01080216 0.00430086 0.00460092 0.013971662 0.019770763 0.022046501 0.024978056 2 46 0.00460092 0.024978056 4 216 0.021604321 0.027588729 1 6 6.00E-04 0.031315108 2 55 0.0055011 0.034651218 REACT_264164 REACT_1949 REACT_2122 REACT_338 REACT_2243 REACT_13594 REACT_13639 REACT_268571 REACT_9029 REACT_1156 REACT_2148 REACT_1364 HSF1-dependent transactivation CDT1 association with the CDC6:ORC:origin complex ChREBP activates metabolic gene expression Transport of Mature mRNAs Derived from Intronless Transcripts Assembly of the prereplicative complex Neurotransmitter uptake and Metabolism In Glial Cells Astrocytic GlutamateGlutamine Uptake And Metabolism Uptake and function of diphtheria toxin Cyclin A:Cdk2associated events at S phase entry Orc1 removal from chromatin Switching of origins to a post-replicative state SLBP Dependent Processing of 2 56 0.00560112 0.035803209 2 58 0.00580116 0.038151276 1 8 8.00E-04 0.041538091 1 9 9.00E-04 0.046609813 2 67 0.00670134 0.049409734 1 10 0.0010002 0.051655201 1 10 0.0010002 0.051655201 1 10 0.0010002 0.051655201 2 70 0.0070014 0.053399718 2 72 0.00720144 0.05612168 2 72 0.00720144 0.05612168 1 11 0.00110022 0.056674389 REACT_150266 REACT_111174 REACT_407 REACT_734 REACT_1725 REACT_7999 REACT_12564 REACT_70 REACT_897 REACT_355141 REACT_1385 REACT_355303 ReplicationDependent Histone Pre-mRNAs Establishment of Sister Chromatid Cohesion Cross-presentation of particulate exogenous antigens (phagosomes) Chk1/Chk2(Cds1) mediated inactivation of Cyclin B:Cdk1 complex DNA Replication PreInitiation M/G1 Transition Removal of the Flap Intermediate from the C-strand AKT phosphorylates targets in the cytosol Removal of the Flap Intermediate G2/M DNA damage checkpoint RHO GTPases Activate NADPH Oxidases Processive synthesis on the lagging strand RHO GTPases activate CIT 1 13 0.00130026 0.066634702 1 13 0.00130026 0.066634702 1 14 0.00140028 0.071576091 2 2 85 85 0.0085017 0.0085017 0.074930155 0.074930155 1 15 0.0015003 0.076491811 1 15 0.0015003 0.076491811 1 18 0.00180036 0.091086257 1 18 0.00180036 0.091086257 1 19 0.00190038 0.0959006 1 20 0.0020004 0.100689921 1 20 0.0020004 0.100689921 REACT_22297 REACT_355377 REACT_355048 REACT_8027 REACT_1768 REACT_264245 REACT_1287 REACT_1439 REACT_264165 REACT_264155 REACT_21352 REACT_312 REACT_571 REACT_125 Heme degradation TP53 Regulates Metabolic Genes Transcriptional Regulation by TP53 Processive synthesis on the C-strand of the telomere Processing of Capped Intronless Pre-mRNA HATs acetylate histones Translesion Synthesis by POLH Common Pathway of Fibrin Clot Formation Chromatin modifying enzymes Chromatin organization RNA Polymerase I/ Mitochondrial Transcription Lagging Strand Synthesis RNA Polymerase III Transcription Initiation From Type 3 Promoter Processing of Capped IntronContaining Pre- 1 20 0.0020004 0.100689921 2 103 0.01030206 0.103713113 2 103 0.01030206 0.103713113 1 21 0.00210042 0.105454347 1 23 0.00230046 0.114909024 2 110 0.0110022 0.115615609 1 24 0.00240048 0.119599526 1 25 0.0025005 0.124265638 3 233 0.023304661 0.126197083 3 233 0.023304661 0.126197083 2 120 0.0120024 0.133186525 1 27 0.00270054 0.133525186 1 28 0.00280056 0.13811887 2 125 0.012502501 0.14219138 REACT_1281 REACT_655 REACT_120919 REACT_263897 REACT_11052 REACT_11066 REACT_355468 REACT_2203 REACT_21391 REACT_1095 REACT_355250 REACT_264464 REACT_281 REACT_7961 REACT_12529 REACT_932 mRNA Transport of Mature Transcript to Cytoplasm Pyrimidine salvage reactions Synthesis of PE Cellular response to heat stress Metabolism of noncoding RNA snRNP Assembly Constitutive Signaling by AKT1 E17K in Cancer G2/M Transition Mitotic G2-G2/M phases Activation of the prereplicative complex Termination of translesion DNA synthesis VEGFA-VEGFR2 Pathway RNA Polymerase III Transcription Initiation Telomere C-strand (Lagging Strand) Synthesis Signaling by VEGF DNA strand 1 29 0.00290058 0.142688657 1 1 30 30 0.0030006 0.0030006 0.14723467 0.14723467 2 128 0.012802561 0.147656839 1 1 31 31 0.00310062 0.00310062 0.151757029 0.151757029 1 2 31 133 0.00310062 0.013302661 0.151757029 0.156861411 2 135 0.013502701 0.160574373 1 33 0.00330066 0.160731269 1 33 0.00330066 0.160731269 2 137 0.013702741 0.164303983 1 35 0.0035007 0.169612336 1 2 1 35 146 38 0.0035007 0.014602921 0.00380076 0.169612336 0.181273616 0.182761311 REACT_107 REACT_6769 REACT_1590 REACT_821 REACT_1371 REACT_22339 REACT_2051 REACT_8030 REACT_355474 REACT_387 REACT_894 REACT_6960 REACT_116145 REACT_953 elongation Apoptotic cleavage of cellular proteins Activation of ATR in response to replication stress G1 Phase Cyclin D associated events in G1 RNA Polymerase III Transcription RNA Polymerase III Abortive And Retractive Initiation Formation of Fibrin Clot (Clotting Cascade) Extension of Telomeres RHO GTPase Effectors Cleavage of Growing Transcript in the Termination Region RNA Polymerase II Transcription Termination Glutathione synthesis and recycling PPARA activates gene expression RNA Polymerase I Transcription 1 38 0.00380076 0.182761311 1 1 39 42 0.00390078 0.00420084 0.187098738 0.19997595 1 42 0.00420084 0.19997595 1 42 0.00420084 0.19997595 1 42 0.00420084 0.19997595 1 42 0.00420084 0.19997595 1 42 0.00420084 0.19997595 3 293 0.029305861 0.202891509 1 43 0.00430086 0.204223714 1 43 0.00430086 0.204223714 1 43 0.00430086 0.204223714 2 169 0.016903381 0.225674211 1 49 0.00490098 0.229249495 REACT_238 REACT_19241 REACT_13565 REACT_9431 REACT_216 REACT_25325 REACT_995 REACT_264041 REACT_9003 REACT_85 REACT_1625 REACT_121256 Initiation Amino acid synthesis and interconversion (transamination) Regulation of lipid metabolism by Peroxisome proliferator-activated receptor alpha (PPARalpha) Regulation of ornithine decarboxylase (ODC) Metabolism of porphyrins DNA Repair AUF1 (hnRNP D0) destabilizes mRNA Apoptotic execution phase Uptake and actions of bacterial toxins SCF(Skp2)-mediated degradation of p27/p21 p53-Dependent G1/S DNA damage checkpoint p53-Dependent G1 DNA Damage Response Phagosomal 1 49 0.00490098 0.229249495 2 172 0.017203441 0.231539899 1 51 0.00510102 0.237418557 1 2 54 183 0.00540108 0.018303661 0.249513109 0.253128156 1 55 0.0055011 0.253502649 1 55 0.0055011 0.253502649 1 56 0.00560112 0.257471379 1 58 0.00580116 0.265346833 1 60 0.0060012 0.273140318 1 1 60 60 0.0060012 0.0060012 0.273140318 0.273140318 REACT_25060 REACT_263923 REACT_169185 REACT_2254 REACT_75820 REACT_7970 REACT_6926 REACT_1974 REACT_957 REACT_75842 REACT_13 REACT_1309 REACT_115639 maturation (early endosomal stage) Iron uptake and transport HDACs deacetylate histones DNA Damage/Telomere Stress Induced Senescence G1/S DNA Damage Checkpoints Class I MHC mediated antigen processing & presentation Telomere Maintenance Glutathione conjugation RNA Polymerase I Promoter Clearance Pyrimidine metabolism Antigen processing: Ubiquitination & Proteasome degradation Metabolism of amino acids and derivatives RNA Polymerase I Transcription Sulfur amino acid 1 61 0.00610122 0.277006584 1 63 0.00630126 0.284678681 1 63 0.00630126 0.284678681 1 63 0.00630126 0.284678681 3 357 0.035707141 0.29368562 1 73 0.00730146 0.321856974 1 74 0.00740148 0.325468821 1 80 0.0080016 0.346746882 1 81 0.00810162 0.350228613 2 235 0.023504701 0.354880769 3 399 0.039907982 0.355054175 1 1 83 84 0.00830166 0.00840168 0.357137542 0.360564926 REACT_169168 REACT_11044 REACT_318 REACT_24994 REACT_1280 REACT_22172 REACT_264487 REACT_121237 REACT_1366 REACT_147723 REACT_467 REACT_1735 REACT_75829 metabolism SenescenceAssociated Secretory Phenotype (SASP) Signaling by Rho GTPases Platelet degranulation Regulation of mRNA stability by proteins that bind AU-rich elements Response to elevated platelet cytosolic Ca2+ Chromosome Maintenance Regulation of HSF1mediated heat shock response Latent infection of Homo sapiens with Mycobacterium tuberculosis RNA Polymerase II Transcription PI3K/AKT Signaling in Cancer mRNA Splicing Major Pathway mRNA Splicing PIP3 activates AKT signaling 1 85 0.0085017 0.363974381 3 406 0.040608122 0.365273502 1 88 0.00880176 0.374096083 1 90 0.0090018 0.380755909 1 95 0.0095019 0.397102794 1 101 0.01010202 0.41616086 1 108 0.01080216 0.437649046 1 109 0.01090218 0.440654746 1 110 0.0110022 0.443644684 1 115 0.0115023 0.45836074 1 1 119 119 0.01190238 0.01190238 0.469858003 0.469858003 1 120 0.0120024 0.472694697 REACT_115961 REACT_355304 REACT_355450 REACT_355160 REACT_355552 REACT_116008 REACT_12464 REACT_12578 REACT_71 REACT_355252 REACT_1505 REACT_22279 REACT_24970 REACT_121401 REACT_111040 REACT_578 REACT_111119 PI3K events in ERBB4 signaling PI-3K cascade:FGFR4 PI-3K cascade:FGFR2 PI-3K cascade:FGFR3 PI-3K cascade:FGFR1 PI3K events in ERBB2 signaling PI3K/AKT activation GAB1 signalosome Gene Expression RHO GTPases Activate Formins Integration of energy metabolism Fatty acid, triacylglycerol, and ketone body metabolism Factors involved in megakaryocyte development and platelet production Glycerophospholipid biosynthesis Signaling by SCFKIT Apoptosis Antigen processing- 1 120 0.0120024 0.472694697 1 120 0.0120024 0.472694697 1 120 0.0120024 0.472694697 1 120 0.0120024 0.472694697 1 120 0.0120024 0.472694697 1 1 1 8 120 123 124 1423 0.0120024 0.01230246 0.01240248 0.142328466 0.472694697 0.481115725 0.483893303 0.487762431 1 135 0.013502701 0.51350012 1 139 0.013902781 0.523847672 2 335 0.033506701 0.533917615 1 150 0.015003001 0.551202842 1 157 0.015703141 0.567801488 1 1 1 168 171 176 0.016803361 0.017103421 0.017603521 0.592675599 0.599212053 0.609878163 REACT_268456 REACT_115596 REACT_252869 REACT_97307 REACT_355063 REACT_355265 REACT_169274 REACT_17025 REACT_118638 REACT_147814 REACT_115755 REACT_355408 REACT_252852 REACT_355289 REACT_355200 REACT_9470 REACT_9417 REACT_147694 REACT_120870 Cross presentation Programmed Cell Death Signaling by ERBB4 Downstream signaling of activated FGFR4 Downstream signaling of activated FGFR3 Downstream signaling of activated FGFR1 Downstream signaling of activated FGFR2 Cellular Senescence Downstream signal transduction Downstream signaling events of B Cell Receptor (BCR) DAP12 signaling Signaling by ERBB2 Signaling by FGFR4 Signaling by FGFR3 Signaling by FGFR1 Signaling by FGFR2 Signaling by FGFR Signaling by EGFR DAP12 interactions Phospholipid metabolism 1 1 179 180 0.017903581 0.018003601 0.61614362 0.618210084 1 182 0.018203641 0.622310321 1 182 0.018203641 0.622310321 1 182 0.018203641 0.622310321 1 1 182 183 0.018203641 0.018303661 0.622310321 0.624344207 1 193 0.019303861 0.644101075 1 1 1 1 1 1 1 1 1 1 195 196 196 196 196 197 199 200 212 213 0.019503901 0.019603921 0.019603921 0.019603921 0.019603921 0.019703941 0.019903981 0.020004001 0.021204241 0.021304261 0.647928296 0.649826735 0.649826735 0.649826735 0.649826735 0.651715129 0.655461992 0.657320564 0.678870512 0.680605104 1 215 0.021504301 0.684046756 REACT_16888 REACT_6959 REACT_12056 REACT_798 REACT_75774 REACT_13477 REACT_355497 REACT_163769 REACT_604 REACT_11061 REACT_13685 REACT_118773 REACT_355457 REACT_12627 REACT_163936 REACT_111217 REACT_13433 REACT_22258 REACT_116125 REACT_6900 Signaling by PDGF Phase II conjugation NGF signalling via TRKA from the plasma membrane Platelet activation, signaling and aggregation Adaptive Immune System Transmission across Chemical Synapses Infectious disease Role of LAT2/NTAL/LAB on calcium mobilization Hemostasis Signalling by NGF Neuronal System Signaling by the B Cell Receptor (BCR) Diseases of signal transduction Generic Transcription Pathway Fc epsilon receptor (FCERI) signaling Metabolism Biological oxidations Metabolism of lipids and lipoproteins Disease Immune System 1 1 224 234 0.022404481 0.023404681 0.699089238 0.714979675 1 241 0.024104821 0.725610084 1 248 0.024804961 0.735851217 4 928 0.092818564 0.736988418 1 2 259 524 0.025905181 0.052410482 0.751191409 0.773316765 1 2 1 1 284 561 327 338 0.028405681 0.056111222 0.032706541 0.033806761 0.782878297 0.805498383 0.828372334 0.838418483 1 357 0.035707141 0.854429165 1 360 0.036007201 0.856810608 2 633 0.063312663 0.856910546 1 11 1 368 2727 455 0.036807361 0.272754551 0.045509102 0.862975824 0.891486119 0.9152958 3 3 4 1107 1146 1601 0.110722144 0.114622925 0.160132026 0.942349953 0.951183852 0.978492444 REACT_15518 REACT_6802 REACT_111102 Transmembrane transport of small molecules Innate Immune System Signal Transduction 1 787 0.078715743 0.987032285 1 4 924 2579 0.092418484 0.25795159 0.994139441 0.999841112