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Supplementary Fig. S1 A.B.. A. Supplementary Fig. S2 B. C.

Published byFelix Marsh Modified over 8 years ago

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Presentation on theme: "Supplementary Fig. S1 A.B.. A. Supplementary Fig. S2 B. C."— Presentation transcript:

1 Supplementary Fig. S1 A.B.

2 A. Supplementary Fig. S2 B. C.

3 A. Supplementary Fig. S3 C.B. D.

4 Supplementary Fig. S4 A.B. C.

5 MMAF-OMe (0.5nM) Downregulated DAP3, RBM3, EEF2, EIF3C, EIF3CL, EIF5, EIF5A, HARS, MRPL13, MRPL16, MRPS15, NACA, RPL23, EIF4A2, EIF4A1 Upregulated FAU, TUFM, RARS2, EEF1D, MRPL15, MRPL18, MRPL24, MRPS16, PTRH2, RPL13, RPL14, RPL18, RPL18A, RPL21P14, RPL22, RPL34, RPL35, RPL36A, RPL36AL, RPS13, RPS14, RPS19, RPS27A, RPS3A MMAF-Ome (5nM) Downregulated DAP3, RBM3, EEF2, EIF5A, MRPL13, MRPL16, MRPL41, MRPL43, PA2G4, RPS21, EIF4A1 Upregulated FAU, RARS2, EIF3L, MRPL15, MRPL18, MRPL3, MRPL9, MRPS7, RPL13, RPL13A, RPL18, RPL18A, RPL19, RPL21P14, RPL24, RPL26, RPL27, RPL30, RPL31, RPL34, RPL35, RPL36A, RPL36AL, RPS13, RPS14, RPS15A, RPS16, RPS26, RPS27A, RPS3A, RPLP0, RPLP1, RPLP2, RPL32 Supplementary Fig. S5 D. MMAF-Ome (1 nM) Downregulated RPLP2 (S102, S105), EIF2S2 (S105, T111), RPLP0 (S304, S307), EIF4ENIF1 (S74, S77), EIF4EBP1 (S65, T68, T70), EIF5B (S134, S135, S137), EEF1B2 (S106), EEF1D (S133), TARBP2 (S152), UPF1 (S1111, S1112), PUM1 (S124) Upregulated RSL1D1 (T423, S427), RPS6 (S235, S236, S240), eEF2 (T54, T57, T59), AKT (S124) 5T4ADC (1  g/ml) Downregulated TARBP2 (S152), EIF4G1 (S1596), EIF4EBP1 (S65, T69, T70), EIF4ENIF1 (S74, S77), EIF2S2 (S105, T111), EIF5 (S389, S390), EIF5B (S134, S135, S137), RPLP2 (S102, S105), EEF1B2 (S106), NGDN (S142, S143), RPLP0 (S304, S307), EEF1D (S133) Upregulated RPS6 (S235, S236, S240), EIF5B (S113, S107), eEF2 (T59) B. C.E. A.

6 Supplementary Fig. S6 A. B.

7 Cell LinesTypeMutations TUM622NSCLC, AA37622 PDX-derivedK-RAS+/- NCI-H1975NSCLC, AdenocarcinomaEGFR+/- (L858R/T790M), PIK3CA+/-(G118D), TP53-/-, CDKN2A-/- Calu-6NSCLCTP53-/-, KRAS+/-, BRCA2+/- NCI-H358NSCLC, Bronchioloalveolar adenocarcinomaKRAS+/-, FGFR1+/- HCC2429NSCLCN.A. MDA-MB-435-5T4Melanoma, pleural effusionBRAF+/-(V600E), TP53+/-, CDKN2A+/- MDA-MB-468Breast, BasalHER2-/ER2-/PrgR-; PTEN-/-, RB1del-/-, SMAD4-/-, TP53-/- MDAMB-361-DYT2Breast, LuminalHER2+/ER2+/PrgR-; 2XPIK3CA+/-, AKT1+/-, EGFR+/- MDA-231Breast, BasalHER2+/ER-/PrgR-; K-RAS+/-, B-RAF+/-, NF2-/-. TP53-/-, CDKN2A-/- CAOV-3Ovarian, AdenocarcinomaTP53-/-, EGFR+/-(R255Q), STK11-/- TOV-112D Ovarian, malignant adenocarcinoma; endometrioid carcinoma TP53-/-, HER2+ OV-90Ovarian, Malignant Papillary Serous AdenocarcinomaTP53-/-, SMAD4-/-. BRAF+/-, CDKN2A-/- OVCAR-3Ovarian, AdenocarcinomaTP53-/-, PPP2R1A+/- SKOV-3Ovarian, AdenocarcinomaPIK3CA+/-(H1047R), TP53-/-, NF1+/-, ATM+/-, APC+/- HT-29Colorectal adenocarcinomaBRAF+/-(V600E), PIK3CA+/-(P449T), SMAD4-/-, TP53-/-, 2XAPC+/- NCI-N87 Gastric carcinoma, Adenocarcinoma, derived from metastatic site, liver SMAD4-/-, TP53-/-, HER2+/-, IL2+/-, PCSK7+/- RajiNHLMYC+/-, TP53+/- Supplementary Table S1

8 Total Proteomics, DAVID ConditionChangeGOCategoryCountP Value MMAF-Ome (0.5 nM)DecreasedGOTERM_BP_ALLtranslation14 5.6E-5 MMAF-Ome (5 nM)DecreasedGOTERM_BP_ALLtranslation101.1E-3 MMAF-Ome (0.5 nM)IncreasedGOTERM_BP_ALLtranslation246.3E-14 MMAF-Ome (5 nM)IncreasedGOTERM_BP_ALLtranslation342.5E-22 Phospho Proteomics, DAVID ConditionChangeGOCategoryCountP Value MMAF-Ome 1 nM DecreasedGOTERM_BP_ALL ribonucleoprotein complex biogenesis 98.7E-4 ribosome biogenesis61.1E-2 Regulation of translation61.8E-2 5T4-ADC 3  g/ml DecreasedGOTERM_BP_ALLRegulation of translation108.3E-4 MMAF-Ome 1 nM IncreasedGOTERM_BP_ALLRNA metabolic process201.2E-4 5T4-ADC 3  g/ml IncreasedGOTERM_BP_ALL Regulation of translation53.9E-2 mRNA metabolic process161.7E-6 Supplementary Table S2A Supplementary Table S2B

9 Fixed Drug RatiosCI Index at ED50 Aur101 : WYE-132HT-29N-87 1:2.70.18 (0.09)0.04 (0.02) 1:8.30.39 (0.04)0.35 (0.04) 1:250.43 (0.04)0.53 (0.28) 1:750.58 (0.02)0.52 (0.12) 1:2250.87 (0.21)0.49 (0.16) 1:6750.57 (0.05)0.41 (0.09) 1:20250.43 (0.07)0.40 (0.13) Supplementary Table S3

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