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ChuData-dependent acquisitionMass SpectrometryBottom-up proteomicsBreast CancerNot availableHsp90Posttranslational modificationsEpichaperomehttps://www.ebi.ac.uk/pride/archive/projects/PXD050251Blood CellEpithelial CellEmbryonic Stem CellBriefly, the digestion mixtures were injected into an Dionex Ultimate 3000 RSLCnano UHPLC system (Dionex Corporation, Sunnyvale, CA), and separated by a 75 μm × 25 cm PepMap RSLC column (100 Å, 2 µm) at a flow rate of ~450 nL min-1. The eluant was connected directly to a nanoelectrospray ionization source of an LTQ Orbitrap XL mass spectrometer (Thermo Scientific, Waltham, MA). LC-MS data were acquired in a data-dependent acquisition mode, cycling between a MS scan (m/z 315–2,000) acquired in the Orbitrap, followed by low-energy CID analysis on three most intense multiply charged precursors acquired in the linear ion trap. For validation experiments in Figure 3e, MS data acquisition and processing were performed as follows. Desalted peptides were concentrated to a very small droplet by vacuum centrifugation and reconstituted in 10 mL 0.1% formic acid in H2O. Approximately 90% of the peptides were analyzed by nano-LC-MS/MS). A Q Exactive HF mass spectrometer was coupled directly to an EASY-nLC 1000 (Thermo Fisher Scientific) equipped with a self-packed 75 mm × 18 cm reverse phase column (ReproSil-Pur C18, 3M, Dr. Maisch GmbH, Germany) for peptide separation. Analytical column temperature was maintained at 50C by a column oven (Sonation GmBH, Germany). Peptides were eluted with a 3-40% acetonitrile gradient over 60 min at a flow rate of 250 nL min-1. The mass spectrometer was operated in DDA mode with survey scans acquired at a resolution of 120,000 (at m/z 200) over a scan range of 300-1750 m/z. Up to 15 of the most abundant precursors from the survey scan were selected with an isolation window of 1.6 Th for fragmentation by higher-energy collisional dissociation with normalized collision energy (NCE) of 27. The maximum injection time for the survey and MS/MS scans was 20 ms and 60 ms, respectively; the ion target value (Automatic Gain Control) for survey and MS/MS scan modes was set to 3e6 and 1e6, respectivelyPride4-tetrahydrothiazine-3-carboxylic acidThe centroided peak lists of the CID spectra were generated using PAVA searched against a database that is consisted of the Swiss-Prot protein database using Batch-Tag, a program of the University of California San Francisco Protein Prospector software, version 5.9.2. For identification of proteins in pull-down experiments, a precursor mass tolerance of 15 ppm and a fragment mass tolerance of 0.5 Da were used for protein database searches (trypsin as enzyme; 1 miscleavage; carbamidomethyl (C) as constant modification; acetyl (protein N-term), acetyl+oxidation (protein N-term), Met-loss (protein N-term), Met-loss+acetyl (protein N-term, oxidation (M)). Protein hits were reported with a Protein Prospector protein score ≥ 22, a protein discriminant score ≥ 0.0 and a peptide expectation value ≤ 0.0197. This set of thresholds of protein identification parameters does not return any substantial false positive protein hits from the randomized half of the concatenated database. After protein identification, PTM search was carried out with S/T/Y phosphorylation included in variable modifications among the identified proteins. A threshold of SLIP score >6 was imposed for false phosphorylation site assignment <5%98. Identified phosphopeptides were manually inspected by confirming the quality of MS/MS spectra and mass accuracy. Cross-linked peptides were identified using an integrated module in Protein Prospector, based on a bioinformation strategy developed in the UCSF Mass Spectrometry Facility43, 44, 99, 100. Key cross-linked peptides were identified and confirmed by manually examining the returned spectrum, peptide scores, mass accuracy and absence from uncross-linked samples.ProteomicsFeixia Chu, Gabriela ChiosisDepartment of Molecular, Cellular & Biomedical Sciences, University of New Hampshire, Durham, NH 03824, USA Chemical Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.PARTIALHomo Sapiens (human)Mus Musculus (mouse)feixia.chu@unh.edu10.1038/S41467-024-53178-539414766 Roychowdhury T, McNutt SW, Pasala C, Nguyen HT, Thornton DT, Sharma S, Botticelli L, Digwal CS, Joshi S, Yang N, Panchal P, Chakrabarty S, Bay S, Markov V, Kwong C, Lisanti J, Chung SY, Ginsberg SD, Yan P, De Stanchina E, Corben A, Modi S, Alpaugh ML, Colombo G, Erdjument-Bromage H, Neubert TA, Chalkley RJ, Baker PR, Burlingame AL, Rodina A, Chiosis G, Chu F. Phosphorylation-driven epichaperome assembly is a regulator of cellular adaptability and proliferation. Nat Commun. 2024 15(1):8912 10.1038/s41467-024-53178-5University of New HampshireUnited StatesThe intricate network of protein-chaperone interactions is crucial for maintaining cellular function. Recent discoveries have unveiled the existence of specialized chaperone assemblies, known as epichaperomes, which serve as scaffolding platforms that orchestrate the reconfiguration of protein-protein interaction networks, thereby enhancing cellular adaptability and proliferation. This study explores the structural and regulatory aspects of epichaperomes, with a particular focus on the role of post-translational modifications (PTMs) in their formation and function. A key finding is the identification of specific PTMs on HSP90, particularly at residues Ser226 and Ser255 within an intrinsically disordered region, as critical determinants of epichaperome assembly. Our data demonstrate that phosphorylation of these serine residues enhances HSP90's interactions with other chaperones and co-chaperones, creating a microenvironment conducive to epichaperome formation. Moreover, we establish a direct link between epichaperome function and cellular physiology, particularly in contexts where robust proliferation and adaptive behavior are essential, such as in cancer and pluripotent stem cell maintenance. These findings not only provide mechanistic insights but also hold promise for the development of novel therapeutic strategies targeting chaperone assemblies in diseases characterized by epichaperome dysregulation, thereby bridging the gap between fundamental research and precision medicine.Phosphorylation-driven epichaperome assembly is a regulator of cellular adaptability and proliferation.Roychowdhury Tanaya T, McNutt Seth W SW, Pasala Chiranjeevi C, Nguyen Hieu T HT, Thornton Daniel T DT, Sharma Sahil S, Botticelli Luke L, Digwal Chander S CS, Joshi Suhasini S, Yang Nan N, Panchal Palak P, Chakrabarty Souparna S, Bay Sadik S, Markov Vladimir V, Kwong Charlene C, Lisanti Jeanine J, Chung Sun Young SY, Ginsberg Stephen D SD, Yan Pengrong P, De Stanchina Elisa E, Corben Adriana A, Modi Shanu S, Alpaugh Mary L ML, Colombo Giorgio G, Erdjument-Bromage Hediye H, Neubert Thomas A TA, Chalkley Robert J RJ, Baker Peter R PR, Burlingame Alma L AL, Rodina Anna A, Chiosis Gabriela G, Chu Feixia Fl(4)17, sodium salt, liquid chromatography tandem mass spectroscopy, l(4)13, IPP2A2, Gli, ammonium formate, 13C-labeled, Egos, cadmium salt, MeCN, Disorders, NCMe, ion, determination, Dissociative Reactions, Cid[Mel], Ci[D], Liquid Chromatography Mass Spectrometry, Design, zinc formate, High Performance Liquid Chromatography Mass Spectrometry, lead salt, Ultra Performance Liquid Chromatography-Mass Spectrometry, magnesium formate, Survey Methods, zinc salt, Questionnaire Designs, CENP-A, vinyl polysiloxane polymer, Long Term, prevention, High Performance Liquid Chromatography-Mass Spectrometry, CENP-C, Hysteria, 5730420M11Rik, peptide, Polypeptides, Techniques, HPLC-MS, ammonium tetraformate, Liquid Chromatography-Mass, peptido, cobalt(II) formate dihydrate, Survey Methodology, CH3-C#N, B1, Min, Nonrespondents, bis(p-chlorophenyl)acetic acid, Randomized Response, Injectables, Effect, prevention and control, N-ethyl O-isopropyl thiocarbamate, DmelCG42273, CG13329, Ultra Performance Liquid Chromatography Mass Spectrometry, SET, Divorced, me75, BcDNA:RE21270, LCMSMS, MACH 2 dental impression material, i2pp2a., peptides, reference sample, TAF-I, hypoplasia, Designs, min, mAPC, Divorces, purification, Questionnaires, copper, SCAN, D17Mit170, T1, AI047805, DmelCG4299, isolation and purification, preventive measures, IGAAD, set, CI, lithium salt, column, Respondents, affinis, DmelCG10574, Liquid Chromatography-Mass Spectrometries, Reaction, D1, Cenp-A, ammonium (2:1) salt, Long-Term Effects, nickel salt, CiD, LC-MS2, phapii, Ce, Questionnaire, Ci, preventive therapy, cobalt (+2) salt, vinyl siloxane, LC-MS/MS, Dmel_CG7826, Longterm Effect, StF-IT-1, Th, Tl3, Questionnaire Design, Tl2, Thermo Scientific, not genetically inherited, collisionally activated dissociation, Cid, CID, ciD, sodium (4:1:1) salt, Dm1, magnesium salt, Ionen, polyvinyl siloxane, Dow Z-200, ci-D, nickel (+2) salt, Dmel_CG7835, cenpA, Mnb, MNB, ammonium salt, HLA-DR-associated protein II, CenH3/CID, Ci/Gli, Ci/GLI, CENP-A/Cid, CENP-A/CID, polyvinyl siloxane polymer, DI-2, High Pressure Liquid Chromatography Mass Spectrometry, MS/MS, CENPA, I-2Dm, Nonrespondent, formate, Spectrometry, cobaltous formate, cromium (+3), CG4299, AW124434, Survey Method, Dissociation, I-2PP1, nanospray, TAF-IBETA, liquid chromatography-tandem mass spectroscopy, copper salt, ammonium (4:1) salt, Surveys, Liquid, TAF-Ibeta, Polypeptide, methyl cyanide, lead (+2) salt, Ci-155, Community, nickel formate dihydrate, lead formate, Dissociative Reaction, Effects, aluminum salt, cesium salt, thomson, polyvinylxiloxane, CG7826, PHAPII, LC-MS-MS, mass-to-charge ratio, formic acid, CenpA, l(4)102ABc, ghenesil, potassium salt, reduced, isolation, Injection, 14C-labeled, Baseline, LC-MSMS, Community Survey, CG7835, Baseline Surveys, CG42273, Survey, Randomized, Low, Randomized Response Techniques, tiny, Separated, Siah, ethylcarbamothioic acid, CenH3[Cid], CenH3[CID], UPLC-MS, Ultra-Performance Liquid Chromatography-Mass Spectrometry, Methodology, anatomical systems, MACH-2, thallium (+1) salt, Self, Longterm, MS2, iones, ipp2a2, rubidium salt, Dissociative Hysteria, DmelCG13329, 2pp2a, Spectrometries, Respondent, Long-Term, calcium formate, methanoic acid, Questionnaires and Surveys, ions, CG10574, X-linked combined immunodeficiency, Injectable, 2PP2A, taf-ibeta, Disorder, dSET, dSet, CG2125, Randomized Response Technique, peptidos, cromium (+3) salt, Long-Term Effect, Chromatography-Mass Spectrometries, sodium formate, PTHB1, Controlled, small, Repeated Rounds of Survey, DYRK1, Controlling, cou, nickel formate, 1-(14)C-labeled, 3H-labeled, Dissociative, igaad, strontium formate, Reprosil, cenH3, High Pressure Liquid Chromatography-Mass Spectrometry, potassium formate, copper (+2) salt, strontium salt, acetonitrile, Peptide, group, polypeptide, LC/MS/MS, Lr, CAD, Temperatures, ci[D], I-2PP2A, Ci155, C18, Hysterias, cupric formate, chemical analysis, Long Term Effects, Dm I-2, I2PP2A, Dyrk1, O-(1-methylethyl) ester, Vacuums, aluminum formate, ACETONITRILE, tandem MS, cyanomethane, Methods, DDA, Community Surveys, AU020952, MACH-2 dental impression material, Response Techniques, Separation, lithium formate, DmelCG2125, CenH3, ci155, Reactions, underdeveloped, ensemble, Response Technique, prophylaxis, Separations, CC1, ethanenitrile, chromic formate, Longterm Effects, ME-IV, Baseline Survey, dSET/TAF-Ibeta, 2610030F17Rik, exafine, Ion, control, Dissociative Disorder, Chromatography-Mass Spectrometry, Z 200, Bra, calcium salt, LC-MS, liquid chromatography tandem mass spectrometry, Peptid, assay, Fugue, AA407739, CenpA/CID, CID/CENP-APhosphorylations, regulator., phosphorylationl(4)17, l(4)13, IPP2A2, Gli, Protein Structure Database, posttranslational modification, E 920, Hgfr, Cid[Mel], Ci[D], 5730555F13Rik, Protein Sequence Database, protein, CENP-A, phosphorylation, CENP-C, ter, 5730420M11Rik, Protein Databases, peptide, Polypeptides, peptido, HGFR, Software Engineering, 2-amino-3-mercaptopropanoic acid, Cystein, Analysis, protein aggregate, Computer Program, WMS, IKKg, KEY, Key, CG13329, Mass Spectrum Analysis, C, SET, posttranslational amino acid modification, BcDNA:RE21270, peptides, Analyses, MUB3_18, TAF-I, cisteina, M, Open, Computer Programs and Programming, MUB3.18, DmelCG4299, IGAAD, set, XRCC7, CI, DmelCG10574, Bsg75C, dxnph, ppm, Cenp-A, Sequence Databases, RG7MT1, GPHYSD2, Racemethionine, SGS, CiD, phapii, Ce, proto-oncogene c-Met, Ci, PRO, 2-Amino-4-(methylthio)butyric acid, StF-IT-1, 9130215G10Rik, CYS, Cys, Spectrum Analysis, collisionally activated dissociation, Source Softwares, Cid, CID, ciD, Software Tools, Programs, ACMICD, Incentive, Spectroscopy, Sequence Database, Program, Computer Applications, DmIKKgamma, batch, Term, dIKK, Computer Applications Software, Kenny, Computer Applications Softwares, ci-D, Methionin, University, Softwares, Hmet, (2R)-2-amino-3-sulfanylpropanoic acid, and GLY protein 2, region, cenpA, parent ion, HGF receptor, HGF/SF receptor, and GLY protein 1, Software Applications, HLA-DR-associated protein II, PTM, CenH3/CID, Ci/Gli, Ci/GLI, Disincentive, CENP-A/Cid, CENP-A/CID, DI-2, MS/MS, CENPA, Source Software, I-2Dm, DNAPK, IKK-gamma, Spectrometry, MASS, CG4299, hCMT1c, c-Met, beta Trypsin, L-Cystein, Protein Sequence, I-2PP1, Applications, TAF-IBETA, DmelCG16910, precursor ion, post-translational modification, Protein Database, Biocatalyst, DOXNPH, TAF-Ibeta, Polypeptide, i2pp2a, Ci-155, Computer Software Applications, Incentives, 2-amino-4-(methylsulfanyl)butanoic acid, Biocatalysts, L-Zystein, FBN, Gene, Database, Computer, precursor, Spectrum Analyses, Protein Structure Databases, protein-containing complex, dIKK-gamma, PHAPII, DNAPDcs, Protein Sequence Databases, CenpA, l(4)102ABc, HGF, ECTOL1, DmIKK-gamma, DNPK1, Gene Products, Mass, F15E12.6, dmIKKgamma, RCCP2, AI326420, IKK[[gamma]], Siah, Application, Mass Spectroscopy, CenH3[Cid], CenH3[CID], DNA-PKcs, Open Source Softwares, F15E12_6, Motivations, scatter factor receptor, Software Application, p460, MS2, E-920, HYRC1, ipp2a2, beta-Trypsin, DmelCG13329, Open Source Software, 2pp2a, SWISS PROT, Hcys, posttranslational protein modification, AUTS9, CG10574, scid, Computer Software Application, OCTD, X-linked combined immunodeficiency, Enzyme, DmelCG4216, 2-amino-4-(methylthio)butanoic acid, 2PP2A, AU019811, Tools, 10^[-6], IKK, CYSTEINE, taf-ibeta, Protein Structure, Structure Database, dSET, dSet, CG2125, FREE CYSTEINE, site, peptidos, slip, AI838057, Disincentives, (2R)-2-amino-3-mercaptopropanoic acid, metionina, TAG, Applications Software, SWISS-PROT, Open Source, Computer Software, DL-Methionine, protein complex, SwissProt, Proteins, igaad, Phosphorylations, cenH3, Peptide, Tool, group, Amino Acid Sequence, polypeptide, IKKgamma, Software Tool, MS, CAD, Phosphopeptide, native protein, ci[D], I-2PP2A, Ci155, Protein, Dm I-2, I2PP2A, MFS1, Amino Acid Sequence Databases, Software, Zystein, tandem MS, Mass Spectrum Analyses, Data Base, WMS2, Met, MET, ATCMPG1, ATCMPG2, covalent modifier, Mass Spectrum, DmelCG2125, PRSS, CenH3, ci155, ensemble, 2-amino-3-sulfanylpropanoic acid, Dmikkgamma, tyrosine-protein kinase Met, Engineering, Tripcellim, CG4216, Databases, L-2-Amino-3-mercaptopropionic acid, (R)-2-amino-3-mercaptopropanoic acid, CG16910, 2-Amino-3-mercaptopropionic acid, post-translational amino acid modification, SSKS., Protein Gene Products, Computer Programs, Gene Proteins, Trypure, dSET/TAF-Ibeta, 2610030F17Rik, Applications Softwares, SSKS, alpha-amino-gamma-methylmercaptobutyric acid, E920, Peptid, Par4, Structure Databases, AA407739, CenpA/CID, 5730455C01Rik, SF receptor, CID/CENP-APost Translational Amino Acid Modification, Hsp86-1, rasGAP, Activity, Laboratory, hspca, Individualized Medicine, postnatal development, 10538, growth and development, protein, Tumor, GAP1, E(sev)3A, Protein Processing, C81438, phosphorylation, Interaction Network, Protein-Protein Interaction Network, 2-Amino-3-hydroxypropionic acid, DmelCG1242, stc, GADPH, AL024080, diseases, CG8893, gap1, LAP-2, symptoms, PKWS, diseases and disorders, LAP2, Research Activity, protein aggregate, FBgn 32821, Laboratory Research, Protein Interaction Map, multicellular organismal biosynthetic process, hsp4, Psychological, Priorities, Post-Translational Protein, HSP82, single-organism biosynthetic process, anon-WO0068693, human disease, Hsp89, Post-Translational, anabolism, Hsp84, Hsp86, Gapd, Hsp90, Psychologic, mip, E(sina)2, Posttranslational Protein Processing, hspc1, l(3)j5C2, HSP90, d-CdGAPr, HSPN, 2-amino-3-hydroxypropanoic acid, malignant neoplasm, Therapies, Medicine, CM-AVM, Hsp82, Homo sapiens disease, Malignancies, Positive, 2610009E16Rik, Research Priority, hspn, DmelCG8893, HSP83, HSP86, Diagnostic Findings, Tumors, HSPCAL1, Therapy, SIGNS SYMPTOMS, HSPCAL4, screening, Post-Translational Modification, Hsp84-1, DESC, Modifications, Adaptive, Research Priorities, 89kDa, CG1242, RASA, Positive Adaptation, Protein-Protein Interaction Maps, 83K HSP, en(lz)3C/4C, Post Translational Modifications, Benign, 3-Hydroxyalanine, Personalized Medicine, git10, sxt, Diseases, GAP, Gap, p120RASGAP, Theranostics., region, Research and Development, ParaT, HSP90N, Ras-GAP, Psychologic Adaptation, CG10538, anon-EST:Liang-2.53, Processing, signs, Benign Neoplasms, HSP90A, gap, Treatments, Adaptation, Malignant Neoplasms, Activities, disease, Amino Acid Modification, Protein Protein Interaction Map, 90kDa, Ras p21 protein activator, L Serine, Posttranslational Modifications, L-Serine, Clinical Finding, 83, Posttranslational Modification, other disease, Post-Translational Protein Modifications, HSP89A, GAPDH II, Neoplasms, Benign Neoplasm, GTPase-activating protein, Gene, Gapdh13F, Network, biosynthesis, AL022974, protein-containing complex, Malignant, Symptoms and Signs, Posttranslational, Protein Interaction Networks, Adjustment, Gene Products, Post Translational Modification, swo1, disease or disorder, Post-Translational Modifications, Precision, Finding, Map, Post Translational, Protein-Protein, Modification, study, hsp90a, Individualized, Malignancy, formation, RasGAP, Research, GA3PDH, ms(3)08445, Gap 1, GAPDH2, Adaptive Behaviors, Psychological Adaptation, Protein Modifications, synthesis, non-neoplastic, Post-Translational Amino Acid Modification, Neoplasias, Gapdh-2, hsp89, Posttranslational Amino Acid Modification, hsp86, hsp84, hsp83, Posttranslational Protein, site, disorder, CG6721, Protein-Protein Interaction Map, hsp90, Development and Research, Predictive, Interaction Map, Cancer, Protein Interaction Network, findings, Malignant Neoplasm, Predictive Medicine, protein complex, Recovery, Proteins, hsp82, disorders, Phosphorylations, Post-Translational Protein Modification, function, medical condition, Positive Adaptations, Personalized, RASGAP, Behavior, Psychological Recoveries, development, Healthy Adaptation, Signs and Symptoms, EL52, Serin, 86kDa, Priority, MT, native protein, Gapdh, Protein, HSPC1, Research Activities, Neoplasm, sequence, Psychological Recovery, condition, clone 2.53, rI533, Protein Modification, p120GAP, 143198_at, GAPDH, anon-WO0140519.209, lap2, primary cancer, DmelCG6721, Post Translational Protein Processing, postnatal growth, DmelCG10538, Healthy Adaptations, Theranostic, Cancers, CMAVM, DMHSP82, malignant tumor, primary structure of sequence macromolecule, HSPCA, Healthy, Protein Gene Products, Su(Raf)3A, Gene Proteins, Adaptive Behavior, Post Translational Protein Modification, Protein Interaction, Protein-Protein Interaction, Hspcb, Therapeutic, P-Health, AL024147, ORF1, Protein Protein Interaction Network, Post-Translational Protein Processing, Hspca, Treatment, P Health, Protein-Protein Interaction Networks, growth, NeoplasiaPost Translational Amino Acid Modification, Hsp86-1, rasGAP, Activity, Laboratory, hspca, Individualized Medicine, postnatal development, Stem Cells, 10538, growth and development, protein, Tumor, GAP1, E(sev)3A, Protein Processing, C81438, phosphorylation, Interaction Network, Protein-Protein Interaction Network, 2-Amino-3-hydroxypropionic acid, DmelCG1242, stc, GADPH, AL024080, diseases, CG8893, Roles, gap1, LAP-2, symptoms, Concepts, PKWS, diseases and disorders, LAP2, Research Activity, protein aggregate, FBgn 32821, Laboratory Research, IKKg, Protein Interaction Map, multicellular organismal biosynthetic process, KEY, Key, hsp4, Psychological, Priorities, Post-Translational Protein, HSP82, single-organism biosynthetic process, anon-WO0068693, human disease, Hsp89, Post-Translational, anabolism, Hsp84, Hsp86, Gapd, Hsp90, Psychologic, mip, E(sina)2, Posttranslational Protein Processing, hspc1, l(3)j5C2, HSP90, d-CdGAPr, HSPN, 2-amino-3-hydroxypropanoic acid, malignant neoplasm, Role Concepts, Therapies, Medicine, CM-AVM, Hsp82, Homo sapiens disease, Malignancies, Positive, 2610009E16Rik, Research Priority, hspn, DmelCG8893, HSP83, HSP86, Diagnostic Findings, Tumors, HSPCAL1, Therapy, SIGNS SYMPTOMS, HSPCAL4, screening, Post-Translational Modification, Hsp84-1, DESC, Modifications, Adaptive, Research Priorities, 89kDa, CG1242, RASA, Positive Adaptation, Protein-Protein Interaction Maps, 83K HSP, DmIKKgamma, en(lz)3C/4C, Post Translational Modifications, Role Concept, Benign, 3-Hydroxyalanine, Stem Cell, dIKK, Personalized Medicine, git10, sxt, Kenny, Diseases, Role, GAP, Gap, p120RASGAP, Theranostics., region, Research and Development, ParaT, HSP90N, Ras-GAP, Psychologic Adaptation, CG10538, anon-EST:Liang-2.53, Processing, IKK-gamma, signs, Benign Neoplasms, HSP90A, gap, Treatments, Adaptation, Malignant Neoplasms, Activities, disease, DmelCG16910, Amino Acid Modification, Protein Protein Interaction Map, 90kDa, Ras p21 protein activator, L Serine, Posttranslational Modifications, L-Serine, Clinical Finding, 83, Posttranslational Modification, other disease, Post-Translational Protein Modifications, HSP89A, GAPDH II, Neoplasms, Benign Neoplasm, GTPase-activating protein, Gene, Gapdh13F, Network, biosynthesis, AL022974, protein-containing complex, Malignant, dIKK-gamma, Symptoms and Signs, Posttranslational, Protein Interaction Networks, Adjustment, DmIKK-gamma, Gene Products, Post Translational Modification, swo1, Pluripotent Stem Cell, disease or disorder, Post-Translational Modifications, Precision, dmIKKgamma, Finding, IKK[[gamma]], Map, Post Translational, Protein-Protein, Modification, study, hsp90a, FOCUS, Individualized, Malignancy, formation, RasGAP, Research, GA3PDH, ms(3)08445, Gap 1, GAPDH2, Adaptive Behaviors, Psychological Adaptation, Protein Modifications, synthesis, non-neoplastic, Post-Translational Amino Acid Modification, Neoplasias, Gapdh-2, IKK, hsp89, Posttranslational Amino Acid Modification, hsp86, hsp84, hsp83, Posttranslational Protein, site, disorder, CG6721, Protein-Protein Interaction Map, hsp90, Development and Research, Predictive, Interaction Map, Cancer, Protein Interaction Network, findings, Malignant Neoplasm, Predictive Medicine, protein complex, Recovery, Proteins, hsp82, disorders, Phosphorylations, Post-Translational Protein Modification, function, medical condition, Positive Adaptations, Pluripotent, Personalized, RASGAP, Behavior, Psychological Recoveries, Concept, development, IKKgamma, Healthy Adaptation, Signs and Symptoms, EL52, Serin, 86kDa, Priority, MT, native protein, PSC cell, Gapdh, Protein, HSPC1, Research Activities, Neoplasm, sequence, Psychological Recovery, condition, clone 2.53, rI533, Protein Modification, p120GAP, 143198_at, GAPDH, anon-WO0140519.209, lap2, primary cancer, DmelCG6721, Dmikkgamma, Post Translational Protein Processing, postnatal growth, DmelCG10538, Healthy Adaptations, Theranostic, Cancers, CG16910, CMAVM, DMHSP82, malignant tumor, primary structure of sequence macromolecule, HSPCA, Healthy, Protein Gene Products, Su(Raf)3A, Gene Proteins, Adaptive Behavior, Post Translational Protein Modification, Protein Interaction, Protein-Protein Interaction, Hspcb, Therapeutic, P-Health, AL024147, ORF1, Protein Protein Interaction Network, Post-Translational Protein Processing, Hspca, Treatment, P Health, Protein-Protein Interaction Networks, growth, NeoplasiaPhosphorylations, regulator., phosphorylationfalsePhosphorylation-Driven Epichaperome Assembly: A Critical Regulator of Cellular Adaptability and ProliferationThe intricate protein-chaperone network is vital for cellular function. Recent discoveries have unveiled the existence of specialized chaperone complexes called epichaperomes, protein assemblies orchestrating the reconfiguration of protein-protein interaction networks, enhancing cellular adaptability and proliferation. This study delves into the structural and regulatory aspects of epichaperomes, with a particular emphasis on the significance of post-translational modifications in shaping their formation and function. A central finding of this investigation is the identification of specific PTMs on HSP90, particularly at serine residues Ser226 and Ser255 situated within an intrinsically disordered region, as critical determinants in epichaperome assembly. Our data demonstrate that the phosphorylation of these serine residues enhances HSP90's interaction with other chaperones and co-chaperones, creating a microenvironment conducive to epichaperome formation. Furthermore, this study establishes a direct link between epichaperome function and cellular physiology, especially in contexts where robust proliferation and adaptive behavior are essential, such as cancer and stem cell maintenance. These findings not only provide mechanistic insights but also hold promise for the development of novel therapeutic strategies targeting chaperone complexes in diseases characterized by epichaperome dysregulation, bridging the gap between fundamental research and precision medicine.2024-10-172024-03-01PXD050251NEWT:330879NEWT:108018NEWT:377960NEWT:1131NEWT:35795NEWT:2042546NEWT:259447NEWT:295546NCBITaxon:2719036NEWT:1334565NEWT:625351NEWT:258594NCBITaxon:1280NEWT:112503NEWT:1129NEWT:309807NEWT:59753NEWT:89184NEWT:309800NEWT:281395NEWT:247480NEWT:1211601NEWT:876138NEWT:44271NEWT:193516NEWT:2315688NEWT:592321NEWT:1073882NEWT:6819NEWT:112509NEWT:46429NEWT:475174NEWT:111205NEWT:1599NEWT:428386NEWT:1117NEWT:498257NEWT:10036NEWT:32264NEWT:12215NEWT:1590NEWT:10034NEWT:33114NEWT:1596NEWT:2736291NEWT:661410NEWT:638632NEWT:224326NEWT:294671NEWT:376619NEWT:1748418NCBITaxon:79857NEWT:1096976NEWT:3765NEWT:3767NEWT:1589NEWT:1907535NEWT:135622NEWT:4615NEWT:672127NEWT:35786NEWT:1580NEWT:399784NEWT:96731NEWT:656061NEWT:37965NEWT:656064NEWT:1582NEWT:3760NEWT:1584NEWT:2086595NEWT:36630NEWT:1585NEWT:383379NEWT:381198NEWT:418106NCBITaxon:12721NEWT:166340NEWT:10029NEWT:913645NEWT:2492962NEWT:641809NEWT:1392488NEWT:38815NEWT:317447NEWT:4688NEWT:3357NEWT:111225NEWT:7719NEWT:29073NEWT:5530NEWT:868565NEWT:135674NEWT:1562698NEWT:79329NEWT:30069NEWT:12637NEWT:59729NEWT:2164133NEWT:295105NEWT:2767846NEWT:108061NEWT:60711NEWT:2020713NEWT:224308NEWT:3347NEWT:49928NEWT:3349NEWT:160621NEWT:2502409NEWT:212790NEWT:110368NEWT:55350NEWT:1916073NEWT:1310161NEWT:77133NEWT:145481NEWT:1310165NEWT:29058NCBITaxon:79824NEWT:468822NEWT:1912919NEWT:410658NEWT:5516NEWT:44688NEWT:44689NEWT:370038NEWT:498211NEWT:345076NEWT:347256NEWT:5518NEWT:398007NEWT:1527468NEWT:498217NEWT:498216NEWT:11320NEWT:246196NEWT:246197NEWT:145458NEWT:1310173NEWT:200795NEWT:37919NEWT:342808NEWT:2579791NEWT:44685NEWT:161934NEWT:156587NEWT:1148NEWT:5508NEWT:3329NEWT:419481NEWT:5507NEWT:260499NEWT:410661NEWT:329854NEWT:1140NCBITaxon:2157NEWT:2066563NEWT:2649329NEWT:1143NEWT:1287689NEWT:1094343NEWT:1462472NEWT:1336795NEWT:644042NEWT:150808NEWT:709964NEWT:1182590NEWT:3712NEWT:3711NEWT:156974NEWT:3714NCBITaxon:37162NEWT:270643NEWT:3715NEWT:1538NEWT:2065263NEWT:199225NEWT:177437NEWT:717966NEWT:9014NEWT:10891NEWT:10418NEWT:118698NEWT:1616117NEWT:118696NEWT:34865NEWT:52283NEWT:28174NEWT:284812NEWT:8175NEWT:43330NEWT:1603293NEWT:29022NEWT:44664NEWT:43346NEWT:3702NEWT:1245466NEWT:3704NEWT:244366NEWT:1246791NEWT:176597NEWT:118694NEWT:2850NEWT:118691NEWT:34871NEWT:9006NEWT:33548NEWT:52299NEWT:1883426NEWT:8165NEWT:96794NEWT:10401NEWT:10886NEWT:3708NEWT:332648NEWT:44670NEWT:926571NEWT:536231NEWT:376219NEWT:219813NEWT:1510NEWT:1955249NEWT:215451NEWT:460519NEWT:1515NEWT:572307NEWT:1432138NEWT:2714896NEWT:1424507NEWT:1194599NEWT:272844NEWT:1348799NEWT:1608994NEWT:33995NEWT:55784NEWT:1303443NEWT:9483NEWT:485NEWT:329032NEWT:56636NEWT:2709072NEWT:2499525NEWT:55307NEWT:1122981NEWT:2853422NEWT:1122984NEWT:487NEWT:1538553NEWT:1679718NEWT:480NEWT:67767NEWT:45972NEWT:46835NEWT:109757NEWT:582580NEWT:1185650NEWT:216778NEWT:294607NEWT:1502NEWT:128017NEWT:2836NEWT:376686NEWT:237610NEWT:95486EFO:0001352NEWT:219809NEWT:219808NEWT:119562NEWT:1883446NEWT:31345NEWT:1233435NEWT:118223NEWT:11757NEWT:141469NEWT:987059NEWT:109760NEWT:29031NEWT:317047NEWT:1509NEWT:491NEWT:460523NEWT:45954NEWT:1578NEWT:235443NEWT:1579NEWT:1757312NEWT:85694NEWT:109786NEWT:1922344NEWT:108458NEWT:5936NEWT:85692NEWT:321967NEWT:320637NEWT:1078283NEWT:3750NEWT:983964NEWT:11706NEWT:32644NEWT:527796NEWT:279010NEWT:291146NEWT:29466NEWT:499175NEWT:109779NEWT:3745NEWT:1715989NCBITaxon:4751NEWT:3747NEWT:1116234NEWT:415978NEWT:235455NEWT:1255228NEWT:410289NEWT:191701NEWT:373153NEWT:1640278NEWT:9054NEWT:472NEWT:940825NEWT:29459NEWT:529507NEWT:1071661NEWT:1380096NEWT:28128NEWT:470NEWT:41122NEWT:5911NEWT:1328300NEWT:748693NCBITaxon:50557NEWT:39251NEWT:29491NEWT:911022NEWT:101841NEWT:446NEWT:153481NEWT:2014887NEWT:717989NEWT:33952NEWT:1255232NEWT:11723NEWT:445NEWT:153009NEWT:1004879NEWT:261756NEWT:166314NEWT:166313NEWT:63366NEWT:63367NEWT:29488NEWT:1871049NEWT:215402NEWT:1547NEWT:1290454NEWT:3726NEWT:906914NEWT:81231006NEWT:156981NEWT:30455NEWT:28141NEWT:9031NEWT:27292NEWT:1050722NEWT:3728NEWT:108931NEWT:1293497NEWT:1055524NEWT:219799NEWT:219798NEWT:548NEWT:150475NEWT:267872NEWT:381666NEWT:172269NEWT:9534NEWT:2126348NEWT:5180NEWT:256737NEWT:299467NEWT:9541NEWT:51350NEWT:8694NEWT:33936NEWT:8692NEWT:542NEWT:2903NEWT:394503NEWT:185579NEWT:872227NEWT:13076NEWT:2587410NEWT:207340NEWT:1006581NEWT:8673NEWT:9527NEWT:33940NEWT:2126337NEWT:550NEWT:253237NEWT:10804NEWT:33941NEWT:554NEWT:451516NEWT:552NEWT:1325291NEWT:42410NEWT:36185NEWT:1054211NEWT:1225786NEWT:771870NEWT:51338NEWT:9995NEWT:575412NEWT:28112NEWT:49495NEWT:49012NEWT:28110NEWT:6493NEWT:10832NEWT:6494NEWT:6491NEWT:507601NEWT:520NEWT:64657NEWT:186441NEWT:643680NEWT:214092NCBITaxon:6157NEWT:40697NEWT:13095NEWT:162425NEWT:104105NEWT:216257NEWT:242124NEWT:9986NEWT:8654NEWT:8658NEWT:1268063NEWT:8657NEWT:9983NEWT:8655NEWT:5147NEWT:595495NEWT:28108NEWT:28104NEWT:1114957NEWT:407821NEWT:691692NEWT:568703NCBITaxon:2NEWT:568708NEWT:1613NEWT:8247NEWT:8245NEWT:986NEWT:52641NEWT:28532NEWT:353152NEWT:298176NEWT:353153NEWT:227377NEWT:1774284NEWT:27689NEWT:207769NEWT:40674NEWT:640131NE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