PXD032216 is an
original dataset announced via ProteomeXchange.
Dataset Summary
Title | CDK6 degradation is counteracted by p16INK4A and p18INK4C in AML |
Description | Cyclin-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. |
HostingRepository | PRIDE |
AnnounceDate | 2022-05-31 |
AnnouncementXML | Submission_2022-05-31_06:17:19.257.xml |
DigitalObjectIdentifier | |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Unsupported dataset by repository |
PrimarySubmitter | Frédéric FONTAINE |
SpeciesList | scientific name: Mus musculus (Mouse); NCBI TaxID: 10090; |
ModificationList | monohydroxylated residue; iodoacetamide derivatized residue |
Instrument | Orbitrap Fusion Lumos |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2022-03-11 09:55:24 | ID requested | |
⏵ 1 | 2022-05-31 06:17:20 | announced | |
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 affiliation | Institute of Pharmacology and Toxicology, University of Veterinary Medicine Vienna, A-1210 Vienna, Austria. |
contact email | Karoline.Kollmann@vetmeduni.ac.at |
lab head | |
Frédéric FONTAINE |
contact affiliation | CeMM Research Center for Molecular Medicine |
contact email | frederic.fontaine.pro@gmail.com |
dataset submitter | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD032216
- Label: PRIDE project
- Name: CDK6 degradation is counteracted by p16INK4A and p18INK4C in AML