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PXD032216

PXD032216 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleCDK6 degradation is counteracted by p16INK4A and p18INK4C in AML
DescriptionCyclin-dependent kinase 6 (CDK6) represents a novel therapeutic target for the treatment of certain subtypes of acute myeloid leukemia (AML). CDK4/6 kinase inhibitors have been widely studied in many cancer types and their effects may be limited by primary and secondary resistance mechanisms. CDK4/6 degraders, which eliminate kinase dependent and kinase independent effects, have been suggested as alternative therapeutic option. We show that efficacy of the CDK6 specific protein degrader BSJ-03-123 varies among AML subtypes and depends on low expression of the INK4 proteins p16INK4A and p18INK4C. INK4 protein levels are significantly elevated in MLL-AF9+ compared to AML1-ETO+ cells, contributing to the different CDK6 degradation efficacy. We demonstrate that CDK6 complexes containing p16INK4A or p18INK4C are protected from BSJ-mediated degradation and that INK4 levels define the proliferative response to CDK6 degradation. These findings define INK4 proteins as predictive marker for CDK6 degradation – targeted therapies in AML.
HostingRepositoryPRIDE
AnnounceDate2022-05-31
AnnouncementXMLSubmission_2022-05-31_06:17:19.257.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterFrédéric FONTAINE
SpeciesList scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationListmonohydroxylated residue; iodoacetamide derivatized residue
InstrumentOrbitrap Fusion Lumos
Dataset History
RevisionDatetimeStatusChangeLog Entry
02022-03-11 09:55:24ID requested
12022-05-31 06:17:20announced
Publication List
Schmalzbauer BS, Thondanpallil T, Heller G, Schirripa A, Sperl CM, Mayer IM, Knab VM, Nebenfuehr S, Zojer M, Mueller AC, Fontaine F, Klampfl T, Sexl V, Kollmann K, in AML. Cancers (Basel), 14(6):(2022) [pubmed]
Keyword List
submitter keyword: CDK6, AML, Degrader, INK4, p16, p18, Cdkn2a, Cdkn2c
Contact List
Karoline Kollmann
contact affiliationInstitute of Pharmacology and Toxicology, University of Veterinary Medicine Vienna, A-1210 Vienna, Austria.
contact emailKaroline.Kollmann@vetmeduni.ac.at
lab head
Frédéric FONTAINE
contact affiliationCeMM Research Center for Molecular Medicine
contact emailfrederic.fontaine.pro@gmail.com
dataset submitter
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Dataset FTP location
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PRIDE project URI
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