PXD042993-1

PXD042993 is an original dataset announced via ProteomeXchange.

Title	Nardilysin-Regulated Scission Mechanism Activates Polo-like Kinase 3 to Suppress the Development of Pancreatic Cancer
Description	Pancreatic ductal adenocarcinoma (PDAC) develops through step-wise genetic and molecular alterations including Kras mutation and inactivation of apoptotic pathways. Here, we find that development of anoikis resistance and metastasis of KrasG12D-driven PDAC in mice is accelerated by deleting Plk3, explaining the often reduced Plk3 expression in human PDAC. Importantly, a 41 kDa Plk3 (p41Plk3) that contained the entire kinase domain at the N-terminus (1-353 aa) is activated by scission of the precursor p72Plk3 at Arg354 by metalloendopeptidase Nardilysin (NRDC), and the resulting p32Plk3 C-terminal Polo-box domain (PBD) was quickly removed by proteasome degradation preventing the p41Plk3 inhibition by PBD. We found that p41Plk3 is the activated form of Plk3 that regulates a feedforward mechanism to promote anoikis and suppress PDAC and metastasis. p41Plk3 phosphorylates c-Fos on Thr164, which in turn, induces expression of Plk3 and pro-apoptotic genes. These findings uncovered an NRDC-regulated post-translational mechanism (PTM) that activates Plk3, establishing a prototypic regulation by scission mechanism.
HostingRepository	PRIDE
AnnounceDate	2023-12-23
AnnouncementXML	Submission_2023-12-23_15:29:29.583.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Paul Chiao
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	phosphorylated residue
Instrument	Voyager-DE PRO

Revision	Datetime	Status	ChangeLog Entry
0	2023-06-14 13:54:01	ID requested
⏵ 1	2023-12-23 15:29:29	announced

Dataset with its publication pending

submitter keyword: Plk3, Nardilysin (NRDC) metalloendopeptidase cleavage, c-Fos, Anoikis, Pancreatic ductal adenocarcinoma (PDAC), Post-translational mechanism (PTM), Genetically engineered mouse models (GEMMs), Plk1, Kinase activation, Metastasis

Paul J Chiao
contact affiliation	Department of Molecular and Cellular Oncology, MD Anderson Cancer Center, Houston, TX USA
contact email	pjchiao@mdanderson.org
lab head
Paul Chiao
contact affiliation	The University of Texas
contact email	pjchiao@mdanderson.org
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/PXD042993

PRIDE project URI

• PRIDE
  1. PXD042993
     1. Label: PRIDE project
     2. Name: Nardilysin-Regulated Scission Mechanism Activates Polo-like Kinase 3 to Suppress the Development of Pancreatic Cancer