PXD032216

PXD032216 is an original dataset announced via ProteomeXchange.

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

Revision	Datetime	Status	ChangeLog Entry
0	2022-03-11 09:55:24	ID requested
⏵ 1	2022-05-31 06:17:20	announced

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]

submitter keyword: CDK6, AML, Degrader, INK4, p16, p18, Cdkn2a, Cdkn2c

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

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2022/04/PXD032216

PRIDE project URI

• PRIDE
  1. PXD032216
     1. Label: PRIDE project
     2. Name: CDK6 degradation is counteracted by p16INK4A and p18INK4C in AML