{"database":"MassIVE","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Other":["ftp://massive-ftp.ucsd.edu/v02/MSV000084551/"]},"type":"primary"},"statusCode":"OK","statusCodeValue":200}],"scores":{"citationCount":0,"reanalysisCount":0,"viewCount":0,"searchCount":0},"additional":{"omics_type":["Proteomics"],"submitter":["Anne-Claude Gingras"],"instrument_platform":["Orbitrap Fusion Lumos"],"species":["Homo Sapiens (ncbitaxon:9606)"],"full_dataset_link":["https://massive.ucsd.edu/ProteoSAFe/dataset.jsp?task=c189e2a5f14144c2ba85bc3b28962a05"],"submitter_email":["gingras@lunenfeld.ca"],"submitter_affiliation":["LTRI"],"sample_protocol":[""],"repository":["MassIVE"],"file_size":["34"],"ptm_modification":["MOD:00685 - \"A protein modification that effectively converts an L-glutamine residue to L-glutamic acid.\"","MOD:00684 - \"A protein modification that effectively converts an L-asparagine residue to L-aspartic acid.\"","MOD:00719 - \"A protein modification that oxygenates an L-methionine residue to one of the diastereomeric L-methionine sulfoxide residues.\""],"data_protocol":[""],"pubmed_abstract":["The RAF family kinases function in the RAS-ERK pathway to transmit signals from activated RAS to the downstream kinases MEK and ERK. This pathway regulates cell proliferation, differentiation and survival, enabling mutations in RAS and RAF to act as potent drivers of human cancers. Drugs targeting the prevalent oncogenic mutant BRAF(V600E) have shown great efficacy in the clinic, but long-term effectiveness is limited by resistance mechanisms that often exploit the dimerization-dependent process by which RAF kinases are activated. Here, we investigated a proteolysis-targeting chimera (PROTAC) approach to BRAF inhibition. The most effective PROTAC, termed P4B, displayed superior specificity and inhibitory properties relative to non-PROTAC controls in BRAF(V600E) cell lines. In addition, P4B displayed utility in cell lines harboring alternative BRAF mutations that impart resistance to conventional BRAF inhibitors. This work provides a proof of concept for a substitute to conventional chemical inhibition to therapeutically constrain oncogenic BRAF."],"pubmed_title":["Functional characterization of a PROTAC directed against BRAF mutant V600E."],"pubmed_authors":["Posternak Ganna G, Tang Xiaojing X, Maisonneuve Pierre P, Jin Ting T, Lavoie Hugo H, Daou Salima S, Orlicky Stephen S, Goullet de Rugy Theo T, Caldwell Lauren L, Chan Kin K, Aman Ahmed A, Prakesch Michael M, Poda Gennady G, Mader Pavel P, Wong Cassandra C, Maier Stefan S, Kitaygorodsky Julia J, Larsen Brett B, Colwill Karen K, Yin Zhe Z, Ceccarelli Derek F DF, Batey Robert A RA, Taipale Mikko M, Kurinov Igor I, Uehling David D, Wrana Jeff J, Durocher Daniel D, Gingras Anne-Claude AC, Al-Awar Rima R, Therrien Marc M, Sicheri Frank F"],"name_synonyms":["dT, p124, anon-74EFc, P-TEFb., DmelCG6292, ORE-14, Dmcyclin T, CG6292"],"description_synonyms":["Goal, Protac, Papers, Publication, Agkistrodon contortrix contortrix protein C activator, Manuscripts, Agkistrodon blomhoffi ussuriensis protein C activator."],"pubmed_title_synonyms":["9930012E13Rik., RAFB1, B-RAF1, C230098H17, Braf-2, Braf2, AA387315, C87398, NS7, AA120551, B-raf, BRAF1, D6Ertd631e, Protac, Agkistrodon contortrix contortrix protein C activator, AA473386, Agkistrodon blomhoffi ussuriensis protein C activator"],"pubmed_abstract_synonyms":["Kinase Kinases, RAS, Ras, DmErk, extracellular signal-regulated kinase activity, l(1)G0098, pp44mapk, DSORT, Kinship, Product, 2410041A17Rik, Tyro5, raf Serine Theonine Protein Kinases, Kinase Cascade, MEK1/2, raf, fs(1)M34, Ras-1, Tumor, ter, Mutations, DmelCG12051, mil-raf Protein Kinases, ras, mil-raf, c-ras2, LeMPK3, p44mpk, Line, Dp38, HEL-176, Life Cycle, CG4601, AA120551, Protein Kinases, Kinase, SAPK2, SEM, Sem, INSL3R, MAP-k, A, C, cyt5C, Kinship Network, Draf-1, MAPK-ERK Kinases, pp42, DHO, JNK Pathway, mil raf Protein Kinases, EK5, MAP Kinase Modules, CG18572, Pathways, Dsor2, JNK Signaling Pathways, DSor1, DSOR1, sem, D-raf1, Map Kinase, Map Kinase Kinase, medicine, Bsg75C, ACT, Act, ATP Phosphotransferases, CG1799, Tumors, ERK-A, Pathway, Degradations, dpERK, dpErk, anatomical protrusion, Ras2, RAS2, l(1)phl, Ras1, RAS1, Actin/BAP47, CTE-II, AACT, ERK-2, CTE-IIa, act, Ach1, hBACH, DmMAPK, ACH1, PMK-2, dp-ERK, PMK-1, PMK-3, act42A, GIG25, raf Proto Oncogene Proteins, Benign, Su(b), Term, p38 Kinase, AFFX-Dros-ACTIN_M_r_at, GIG24, dRas85D, MAP Kinase Kinases, pMAPK, pMapK, Cellular, actin, DMEK-1, ras1, LACH, ras2, BcDNA:RE36103, EK1-1, LGR8, Lgr8, DmERKA, l(1)pole hole, DmelCG4027, rl/MAPK, death rate, Protein Digestions, Hras-1, Benign Neoplasms, Dm Ras1, l(2)41Ac, l(1)polehole, D-raf, human, Agkistrodon blomhoffi ussuriensis protein C activator, C78273, Malignant Neoplasms, RasI, CT34260, actin5C, dpERk, MAPK-ERK, antagonists and inhibitors, Proliferation, SAPK, raf Kinase, Afr-1, EG:BACH48C10.3, MAP Kinase Signaling Cascade, BACH, Harvey-ras, MAP Kinase Cascades, JNK Signaling Pathway, humans, AA473386, Hras1, MAPK Kinases, 9030612K14Rik, l(1)Ab, Act5c, Hybrids, MEKs, p38 Kinase Pathways, dRas, MAPK-ERK Kinase, Neoplasms, raf MAP Kinase Kinase Kinases, MEK-ERK, CG1167, 12559, DRaf, H-ras, ACT5C, DRAS1, DRas2, IMPDH, AFR1, Afr1, Bach, draf, LD06825, EK2-1, Human, Dras2, Dras1, AA407128, D-Ras, Kras-2, Prkm1, Cell growth-inhibiting gene 24|25 protein, raf Proto-Oncogene Proteins, Number Growth, IMPdH, Ha-ras, Man, D-RAF, D-Raf, MAP, Map, ERK, Erk, Dras, PRKM1, ras 1, MEK-ERK Pathway, PRKM2, mKIAA0854, Proto-Oncogene Proteins raf, raspberry/impd, BRWS2, PCBC, C87398, Phl, MEK 7, Ras[V12], Proto-Oncogene Proteins, EK3-4, erk, DRas, fs(1)829, DRas85D/Ras, Neoplasias, Dmras64B, anon-EST:fe2D2, drugs, DmelCG4216, Kinase Kinase, DmelCG18572, Proto Oncogene Proteins raf, Draf, rll, T11, STK26, SOR, Sor, p38-2, Act-5C, Kinase Pathways, myelin basic protein kinase activity, GPR106, Cancer, Pharmaceuticals, inhibitors, Products, 42A, DRT, CPS, Malignant Neoplasm, Family 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Pharmaceutical Product, Cell Number Growth, Su(Raf)34B, mitogen-activated protein kinase activity, mpk1, MIL-RAF Proteins, D-Ras1, p38 Kinase Pathway, Family Life Cycle, Growth, Erk/Map kinase, RTK, Man (Taxonomy), ATP-dependent proteolysis, MIL RAF Proteins, l(1)G0436, DERK-A, ras85B, ras85D, E(sina)7, Rl, Protein Degradation, 9930012E13Rik, GREAT, MP kinase activity, DERK, D-ras-2, C230098H17, act 42A, Pharmaceutical, Ac5C, MBP kinase II activity, CG4027, Great, dERK, Malignancies, D6Ertd631e, Family Life Cycles, dSor1, ERK Pathways, ATP, l(3)s1747, MAP kinase 2 activity, B-RAF1, l(1)G0330, SAPKK4, sor/MEK1, D-sor-1, Mapk, Ki-ras, Modern, KIAA0854, DSor, Erk1, ERK1, ERK2, mapk1a, Signaling Pathways, Erk2, LACH1, DRODSOR1, ZHX2, raf Serine-Theonine Protein Kinases, p41mapk, Alpha-1-antichymotrypsin His-Pro-less, mapk1b, MapK, Digestion, MAPK, Signaling Pathway, DFNA26, p21[Ras1], Pharmaceutic, dRas1, dRAS1, Filiation, DRaf1, Dras85D, Mitogen Activated Protein Kinase Kinase, erk2, GAT, 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D-Sor, Xp42, antagonists, DmelCG15793, l(1)G0079, MAPKK, Kinase Pathway, Kinases, mitogen activated kinase activity, Su(Raf)2B, VSCM, act 5C, SAPKK-4, EY2-2, MAPK2, l(1)ph, LGR8.1, Su(tor)3-2, 11-29, Drug, Preparations, D-ERK, Braf-2, ERT1, EPHT3, Modern Man, Cell Multiplication, Raf, RAF, Actin5C, Agkistrodon contortrix contortrix protein C activator, MAP kinase 1 activity, Pharmaceutical Preparation, CG2845"],"citation_count":["0"],"additional_accession":[]},"is_claimable":false,"name":"Posternak_PROTACagainstBRAFV600E_P124_Lumos","description":"The files are associated with a manuscript submitted for publication by Ganna Posternak et al. The main goal of this paper was functionally characterize the mechanism of action of a PROTAC designed to target BRAFV600E.","dates":{"publication":"Thu Nov 07 12:23:00 GMT 2019"},"accession":"MSV000084551","cross_references":{"pubmed":["32778845"]}}