PXD042993

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

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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