{"database":"Pride","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Tabular":["ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2026/06/PXD067076/ip-esf_549_73-96-rerun_esf6_diann_directdia_20250707.pr_matrix_edit.tsv"],"Other":["ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2026/06/PXD067076/esf6_05241_Slot1-15_1_8752.d.zip","ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2026/06/PXD067076/esf6_05238_Slot1-12_1_8749.d.zip","ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2026/06/PXD067076/esf6_05193_Slot1-28_1_8691.d.zip","ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2026/06/PXD067076/esf6_05190_Slot1-25_1_8688.d.zip","ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2026/06/PXD067076/esf6_05240_Slot1-14_1_8751.d.zip","ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2026/06/PXD067076/esf6_05239_Slot1-13_1_8750.d.zip","ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2026/06/PXD067076/esf6_05192_Slot1-27_1_8690.d.zip","ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2026/06/PXD067076/esf6_05191_Slot1-26_1_8689.d.zip"]},"type":"primary"},"statusCodeValue":200,"statusCode":"OK"}],"scores":null,"additional":{"labhead_mail":["eric_fischer@dfci.harvard.edu"],"submitter":["Eric Fischer"],"technology_type":["Mass Spectrometry","Data-independent acquisition"],"software":[""],"submitter_keywords":[""],"full_dataset_link":["https://www.ebi.ac.uk/pride/archive/projects/PXD067076"],"tissue":["Cell Culture"],"sample_protocol":["Frozen cells were resuspended in lysis buffer (50 mM Tris pH 8.0, 200 mM NaCl, 2 mM TCEP, 0.1% NP-40, 2 µL Benzonase (EMD Millipore 77664-3), and one tablet of cOmplete protease inhibitor cocktail). The suspension was sonicated on ice for 20 cycles (3 s on, 5 s off) at 25% amplitude. After centrifugation,  bait proteins (15 µM) were added to clarified lysate. Then, the lysate–protein mixture was added to each well of the pre-plated 96-well PCR plate containing compounds. The plate was incubated on ice for 1 hour, followed by addition of 50 µL pre-washed MagStrep® Strep-Tactin®XT beads (IBA 2-5090-010) to each well (final composition: 90 µL lysate, 6 µL compound pool, 25 µL protein, 50 µL resin; final concentration of each drug: 1.1 µM). The mixture was incubated for an additional hour on ice. Beads were washed using wash buffer (50 mM Tris pH 8.0, 2 mM TCEP) containing the corresponding compound pool, and elution was performed using 0.5 M NaOH. The eluate was immediately neutralized with 0.1 M Tris pH 2.0 to achieve a final pH of 8.5 and a final volume of 200 µL. Samples were reduced with TCEP (final concentration 10 mM) for 30 minutes at room temperature on a thermomixer, followed by alkylation with iodoacetamide (Sigma I1149, final concentration 15 mM) for 45 minutes, protected from light. The reaction was quenched with 1 M DTT (final concentration 10 mM). Subsequently, proteins were digested with 3 µg of Trypsin/Lys-C Mix, Mass Spec Grade (Promega V5072) overnight at 37 °C. Sample digests were acidified with formic acid to a pH of 2-3 prior to desalting using C18 solid phase extraction plates (Thermo Scientific 60307). Desalted peptides were dried in a vacuum-centrifuged and reconstituted in 0.1% formic acid for LC-MS analysis."],"repository":["Pride"],"modification":[""],"quantification_method":["Not available"],"data_protocol":["Data were collected using a TimsTOF Ultra2 (Bruker Daltonics, Bremen, Germany) coupled to a nanoElute2 LC pump (Bruker Daltonics, Bremen, Germany) via a CaptiveSpray nano-electrospray source. Peptides were separated on a reversed-phase C18 column (25 cm x 75 µm ID, 1.6 µM, IonOpticks, Australia) containing an integrated captive spray emitter. Peptides were separated using a 50 min gradient of 2 - 30% buffer B (acetonitrile in 0.1% formic acid) with a flow rate of 250 nL/min and column temperature maintained at 50 ºC. The TIMS elution voltages were calibrated linearly with three points (Agilent ESI-L Tuning Mix Ions; 622, 922, 1,222 m/z) to determine the reduced ion mobility coefficients (1/K0). To perform diaPASEF, we used py_diAID (Skowronek et al., 2022), a python package, to assess the precursor distribution in the m/z-ion mobility plane to generate a diaPASEF acquisition scheme with variable window isolation widths that are aligned to the precursor density in m/z. Data was acquired using twenty cycles with three mobility window scans each (creating 60 windows) covering the diagonal scan line for doubly and triply charged precursors, with singly charged precursors able to be excluded by their position in the m/z-ion mobility plane. These precursor isolation windows were defined between 350 - 1250 m/z and 1/k0 of 0.6 - 1.45 V.s/cm2. The diaPASEF raw file processing and controlling peptide and protein level false discovery rates, assembling proteins from peptides, and protein quantification from peptides were performed either a targeted cell line specific spectral libraries generated by searching using library free analysis in DIA-NN 1.8 (Demichev et al., 2020).The search results are then used to generate a spectral library which is then employed for the targeted analysis of the DIA data searched against a Swissprot human database (January 2021). Database search criteria largely followed the default settings for directDIA including: tryptic with two missed cleavages, carbamidomethylation of cysteine, and oxidation of methionine and precursor Q-value (FDR) cut-off of 0.01. Precursor quantification strategy was set to Robust LC (high accuracy) with RT-dependent cross run normalization. Resulting data was filtered to only include proteins that had a minimum of 3 counts in at least 4 replicates of each independent comparison of treatment sample to the DMSO control. Protein abundances were globally normalized using in-house scripts in the R framework (R Development Core Team, 2014). Proteins with missing values were imputed by random selection from a Gaussian distribution either with a mean of the non-missing values for that treatment group or with a mean equal to the median of the background (in cases when all values for a treatment group are missing). Protein abundances were scaled and significant changes comparing the relative protein abundance of these treatment to DMSO control comparisons were assessed by moderated t-test as implemented in the limma package within the R framework."],"omics_type":["Proteomics"],"labhead":["Eric Fischer"],"instrument_platform":[""],"labhead_affiliation":["Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02215, USA., Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA"],"submission_type":["PARTIAL"],"species":["Homo Sapiens (human)"],"submitter_mail":["eric_fischer@dfci.harvard.edu"],"publication":["Not available"],"submitter_affiliation":["Dana-Farber Cancer Institute"],"submitter_country":["United States"],"additional_accession":[]},"is_claimable":false,"name":"DCAF11-dependent molecular glue degrader activated by glutathionylation","description":"Targeted protein degradation is a powerful pharmacological strategy that harnesses the ubiquitin proteasome system to eliminate disease-relevant proteins, including otherwise undruggable proteins. Here, we report an unbiased and broadly applicable platform for the systematic discovery of molecular glues across diverse E3 ligases. Using multiplexed mass spectrometry-based chemical screening, we identified a molecular glue, M12, that reprograms the E3 ligase DCAF11 to degrade DDX18. We found that M12 functions as a prodrug, activated by glutathionylation. The glutathione moiety then directly engages DCAF11, enabling neo-substrate recruitment. We demonstrate that this mechanism readily enables targeted degradation of a range of proteins. Our studies highlight a novel approach to redirect E3 ligase function through an enzyme-activated small molecule, expanding the scope of targeted protein degradation and chemically induced proximity.","dates":{"publication":"2026-06-18","submission":"2025-08-07"},"accession":"PXD067076","cross_references":{"TAXONOMY":["NEWT:330879","NEWT:377960","NEWT:2042546","NEWT:259447","NEWT:295546","NCBITaxon:2719036","NCBITaxon:1280","NEWT:112503","NEWT:1129","NEWT:309807","NEWT:59753","NEWT:89184","NEWT:309800","NEWT:281395","NEWT:1211601","NEWT:876138","NEWT:44271","NEWT:193516","NEWT:1073882","NEWT:475174","NEWT:111205","NEWT:1117","NEWT:498257","NEWT:10036","NEWT:1590","NEWT:10034","NEWT:661410","NEWT:638632","NEWT:224326","NEWT:376619","NCBITaxon:79857","NEWT:1096976","NEWT:1589","NEWT:135622","NEWT:35786","NEWT:1580","NEWT:399784","NEWT:96731","NEWT:656064","NEWT:383379","NEWT:418106","NEWT:10029","NEWT:913645","NEWT:641809","NEWT:38815","NEWT:317447","NEWT:4688","NEWT:111225","NEWT:7719","NEWT:868565","NEWT:135674","NEWT:79329","NEWT:30069","NEWT:12637","NEWT:59729","NEWT:2164133","NEWT:295105","NEWT:108061","NEWT:60711","NEWT:224308","NEWT:3347","NEWT:160621","NEWT:212790","NEWT:110368","NEWT:1310161","NEWT:77133","NEWT:145481","NEWT:1310165","NEWT:29058","NCBITaxon:79824","NEWT:44688","NEWT:44689","NEWT:498211","NEWT:347256","NEWT:5518","NEWT:398007","NEWT:1527468","NEWT:498217","NEWT:498216","NEWT:11320","NEWT:246196","NEWT:246197","NEWT:145458","NEWT:44685","NEWT:161934","NEWT:1148","NEWT:5508","NEWT:3329","NEWT:419481","NEWT:5507","NEWT:410661","NEWT:1140","NCBITaxon:2157","NEWT:1143","NEWT:1287689","NEWT:1094343","NEWT:1462472","NEWT:1336795","NEWT:644042","NEWT:1182590","NEWT:3712","NEWT:3711","NEWT:270643","NEWT:2065263","NEWT:177437","NEWT:10418","NEWT:118698","NEWT:1616117","NEWT:118696","NEWT:34865","NEWT:52283","NEWT:284812","NEWT:8175","NEWT:43330","NEWT:1603293","NEWT:44664","NEWT:43346","NEWT:3702","NEWT:1245466","NEWT:244366","NEWT:1246791","NEWT:118694","NEWT:2850","NEWT:118691","NEWT:34871","NEWT:33548","NEWT:52299","NEWT:8165","NEWT:96794","NEWT:3708","NEWT:332648","NEWT:44670","NEWT:536231","NEWT:376219","NEWT:219813","NEWT:1510","NEWT:460519","NEWT:1515","NEWT:572307","NEWT:1432138","NEWT:1424507","NEWT:1194599","NEWT:272844","NEWT:1303443","NEWT:9483","NEWT:485","NEWT:56636","NEWT:2853422","NEWT:1679718","NEWT:480","NEWT:67767","NEWT:46835","NEWT:109757","NEWT:582580","NEWT:1185650","NEWT:216778","NEWT:294607","NEWT:1502","NEWT:128017","NEWT:376686","NEWT:95486","NEWT:1883446","NEWT:1233435","NEWT:109760","NEWT:29031","NEWT:317047","NEWT:460523","NEWT:235443","NEWT:1757312","NEWT:85694","NEWT:108458","NEWT:5936","NEWT:320637","NEWT:1078283","NEWT:3750","NEWT:983964","NEWT:11706","NEWT:32644","NEWT:527796","NEWT:499175","NEWT:109779","NEWT:3745","NEWT:1715989","NCBITaxon:4751","NEWT:3747","NEWT:1116234","NEWT:1255228","NEWT:410289","NEWT:373153","NEWT:472","NEWT:940825","NEWT:529507","NEWT:1071661","NEWT:470","NEWT:5911","NCBITaxon:50557","NEWT:39251","NEWT:29491","NEWT:101841","NEWT:446","NEWT:153481","NEWT:2014887","NEWT:33952","NEWT:445","NEWT:153009","NEWT:261756","NEWT:166313","NEWT:63366","NEWT:63367","NEWT:215402","NEWT:1547","NEWT:906914","NEWT:9031","NEWT:27292","NEWT:1050722","NEWT:108931","NEWT:1293497","NEWT:1055524","NEWT:150475","NEWT:267872","NEWT:172269","NEWT:9534","NEWT:5180","NEWT:256737","NEWT:9541","NEWT:8694","NEWT:33936","NEWT:8692","NEWT:2903","NEWT:185579","NEWT:13076","NEWT:1006581","NEWT:8673","NEWT:33940","NEWT:550","NEWT:554","NEWT:451516","NEWT:552","NEWT:1325291","NEWT:36185","NEWT:1054211","NEWT:1225786","NEWT:51338","NEWT:575412","NEWT:28112","NEWT:6493","NEWT:6494","NEWT:6491","NEWT:507601","NEWT:520","NEWT:186441","NEWT:643680","NEWT:214092","NCBITaxon:6157","NEWT:13095","NEWT:162425","NEWT:104105","NEWT:216257","NEWT:9986","NEWT:8654","NEWT:8658","NEWT:1268063","NEWT:8657","NEWT:9983","NEWT:8655","NEWT:5147","NEWT:28108","NEWT:28104","NEWT:407821","NEWT:568703","NCBITaxon:2","NEWT:568708","NEWT:986","NEWT:52641","NEWT:28532","NEWT:353152","NEWT:298176","NEWT:40674","NEWT:1194669","NEWT:51329","NEWT:443906","NEWT:519","NEWT:2510939","NEWT:7394","NEWT:6063","NEWT:1328388","NEWT:1548728","NEWT:667127","NEWT:9557","NEWT:377586","NEWT:300641","NEWT:39655","NEWT:9554","NEWT:38323","NEWT:475932","NEWT:256318","NEWT:206411","NCBITaxon:6191","NEWT:229533","NEWT:214053","NEWT:80863","NEWT:90675","NEWT:52638","NEWT:57075","NEWT:1666905","NEWT:8697","NEWT:8695","NEWT:884204","NEWT:1123869","NEWT:9544","NEWT:9545","NEWT:979","NEWT:7370","NEWT:83906","NEWT:99488","NEWT:1134506","NEWT:255470","NEWT:38783","NEWT:6426","NEWT:33090","NEWT:9935","NEWT:287889","NEWT:305959","NEWT:13489","NEWT:29829","NEWT:92867","NEWT:92866","NCBITaxon:3055","NEWT:51750","NEWT:202950","NEWT:295027","NCBITaxon:11320","NEWT:632957","NEWT:9925","NCBITaxon:9606","NEWT:90690","NEWT:1436183","NEWT:300273","NEWT:4232","NEWT:416348","NEWT:11298","NEWT:4236","NEWT:7742","NEWT:196627","NEWT:200308","NEWT:200302","NEWT:870435","NEWT:9913","NEWT:9915","NEWT:105841","NEWT:2666255","NEWT:999810","NCBITaxon:5693","NEWT:28995","NEWT:1392998","NEWT:380394","NEWT:226900","NEWT:1266738","NEWT:2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