PXD046000

PXD046000 is an original dataset announced via ProteomeXchange.

Title	A PTPB1-Cdk3 signaling axis promotes cell cycle progression of human glioblastoma cells through an Rb-E2F dependent pathway
Description	Protein tyrosine phosphatase 1B (PTP1B) plays a key role in developing different types of cancer. However, the molecular mechanism underlying this effect is unclear. To identify possible molecular targets of PTP1B that mediate its positive role in tumorigenesis, we undertook a SILAC-based phosphoproteomic approach, which allowed us to identify the Cyclin-dependent kinase 3 (Cdk3) as a novel PTP1B substrate. Molecular docking studies revealed stable interactions between the PTP1B catalytic domain and Cdk3. In addition, we observed that PTP1B dephosphorylates Cdk3 at Tyrosine residue 15 in vitro and interacts with it in the nucleus and cytoplasm of human glioblastoma (GB) cells. Finally, we found that the pharmacological inhibition of PTP1B or its depletion with siRNA leads to cell cycle arrest with the diminished activity of Cdk3, the consequent hypophosphorylation of Rb, and the down-regulation of E2F and its target genes Cdk1, Cyclin A, and Cyclin E1. These data delineate a novel signaling pathway from PTP1B to Cdk3 required for efficient cell cycle progression in an Rb-E2F dependent manner in human GB cells and suggest new therapeutic strategies for treating these tumors.
HostingRepository	PRIDE
AnnounceDate	2023-12-05
AnnouncementXML	Submission_2023-12-05_14:09:18.824.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Jonathan Chernoff
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	phosphorylated residue
Instrument	LTQ Orbitrap Velos

Revision	Datetime	Status	ChangeLog Entry
0	2023-10-09 09:56:43	ID requested
⏵ 1	2023-12-05 14:09:19	announced

10.1080/10985549.2023.2273193;

submitter keyword: PTPB1, Glioblastoma, CDK3

Jonathan Chernoff, MD, PhD
contact affiliation	Cancer Signaling and Epigenetics Program, Fox Chase Cancer Center, Phialdelphia, PA, USA
contact email	Jonathan.Chernoff@fccc.edu
lab head
Jonathan Chernoff
contact affiliation	Fox Chase Cancer Center
contact email	J_Chernoff@fccc.edu
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/2023/12/PXD046000

PRIDE project URI

• PRIDE
  1. PXD046000
     1. Label: PRIDE project
     2. Name: A PTPB1-Cdk3 signaling axis promotes cell cycle progression of human glioblastoma cells through an Rb-E2F dependent pathway