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PXD019585 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleProteomics analysis with the Aurora-A PROTAC, JB170
DescriptionThe mitotic kinase Aurora-A is essential for cell cycle progression and considered a priority cancer target. Dozens of ongoing clinical trials are testing the anti-cancer potential of Aurora-A kinase inhibitors. While the catalytic activity of Aurora-A is essential for its function during mitosis, a growing body of evidence indicates an additional non-catalytic function, which is difficult to target by kinase inhibitors. We therefor developed a series of degrader molecules by connecting a kinase inhibitor of Aurora-A to the Cereblon-binding molecule thalidomide. One degrader, JB170, induced the rapid degradation of Aurora-A. We were able to show that JB170 mediated depletion is highly specific for Aurora-A, as degrader mediated complex formation is supported by cooperative binding between Cereblon and Aurora-A. Strikingly, JB-170 mediated depletion caused a strong S-phase arrest, which is not the cell cycle effect observed as a result of Aurora-A kinase inhibition, supporting an important non-catalytic role of Aurora-A during DNA replication. Finally, depletion of Aurora-A resulted in strong induction of apoptosis in various cancer cell lines. The tool compound JB170 presents a versatile starting point for developing new therapeutic drugs to counter Aurora-A function in cancer. In the presented datasets, we determined i) the binding selectivity profile of the Aurora-A PROTAC (JB170) using Kinobeads affinity matrix and ii) its intracellular degradation specificity. We therefore treated IMR5 cells with JB170, the inactive version JB211, or Alisertib and quantified the induced degradation using tandem mass tags.
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterStephanie Heinzlmeir
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListphosphorylated residue; acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
InstrumentOrbitrap Fusion Lumos
Dataset History
RevisionDatetimeStatusChangeLog Entry
02020-06-04 06:31:07ID requested
12020-09-28 06:26:35announced
Publication List
Dataset with its publication pending
Keyword List
submitter keyword: Proteomics analysis with the Aurora-A PROTAC, JB170
Contact List
Prof. Dr. Bernhard Kuster
contact affiliationTechnical University of Munich Chair of Proteomics and Bioanalytics Emil-Erlenmeyer-Forum 5 85354 Freising, Germany
contact emailkuster@tum.de
lab head
Stephanie Heinzlmeir
contact affiliationChair of Proteomics and Bioanalytics, Technische Universit√§t M√ľnchen, Germany
contact emailstephanie.heinzlmeir@tum.de
dataset submitter
Full Dataset Link List
Dataset FTP location
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