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PXD032810

PXD032810 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleUSP28 enables oncogenic transformation of respiratory cells and its inhibition potentiates molecular therapy targeting mutant EGFR, BRAF and PI3K.
DescriptionOncogenic transformation of lung epithelial cells is a multi-step process, frequently starting with the inactivation of tumor suppressors and subsequent activating mutations in proto-oncogenes, such as members of the PI3K or MAPK family. Cells undergoing transformation have to adjust to changes, such as metabolic requirements. This is achieved, in part, by modulating the protein abundance of transcription factors, which manifest these adjustments. Here, we report that the deubiquitylase USP28 enables oncogenic reprogramming by regulating the protein abundance of proto-oncogenes, such as c-JUN, c-MYC, NOTCH and ∆NP63, at early stages of malignant transformation. USP28 is increased in cancer compared to normal cells due to a feed-forward loop, driven by increased amounts of oncogenic transcription factors, such as c-MYC and c-JUN. Irrespective of oncogenic driver, interference with USP28 abundance or activity suppresses growth and survival of transformed lung cells. Furthermore, inhibition of USP28 via a small molecule inhibitor reset the proteome of transformed cells towards a ‘pre-malignant’ state, and its inhibition cooperated with clinically established compounds used to target EGFRL858R, BRAFV600E or PI3KH1047R driven tumor cells. Targeting USP28 protein abundance already at an early stage via inhibition of its activity therefore is a feasible strategy for the treatment of early stage lung tumours and the observed synergism with current standard of care inhibitors holds the potential for improved targeting of established tumors.
HostingRepositoryPRIDE
AnnounceDate2022-04-08
AnnouncementXMLSubmission_2022-04-08_03:44:49.395.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterSüleyman Bozkurt
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListTMT6plex-126 reporter+balance reagent acylated residue; monohydroxylated residue; acetylated residue; iodoacetamide derivatized residue
InstrumentOrbitrap Fusion Lumos
Dataset History
RevisionDatetimeStatusChangeLog Entry
02022-03-25 05:13:47ID requested
12022-04-08 03:44:50announced
Publication List
Prieto-Garcia C, Hartmann O, Reissland M, Braun F, Bozkurt S, Pahor N, Fuss C, Schirbel A, Sch, ü, lein-V, ö, lk C, Buchberger A, Calzado Canale MA, Rosenfeldt M, Dikic I, M, ü, nch C, Diefenbacher ME, USP28 enables oncogenic transformation of respiratory cells, and its inhibition potentiates molecular therapy targeting mutant EGFR, BRAF and PI3K. Mol Oncol, 16(17):3082-3106(2022) [pubmed]
Keyword List
submitter keyword: USP28, c-MYC, c-JUN, lung cancer, EGFR, PIK3CA, BRAF, HRAS Gefitinib, Buparlisib, Vemurafenib
Contact List
Christian Münch
contact affiliationInstitute of Biochemistry II, Faculty of Medicine, Goethe University, Frankfurt am Main, Germany Frankfurt Cancer Institute, Frankfurt am Main, Germany Cardio-Pulmonary Institute, Frankfurt am Main, Germany
contact emailch.muench@em.uni-frankfurt.de
lab head
Süleyman Bozkurt
contact affiliationInstitute of Biochemistry II, Goethe University Frankfurt, Theodor-Stern-Kai 7, Haus 75 60590 Frankfurt am Main
contact emailbozkurt@med.uni-frankfurt.de
dataset submitter
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Dataset FTP location
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