PXD014577

PXD014577 is an original dataset announced via ProteomeXchange.

Title	Global analysis of protein degradation rates during prion infection
Description	Prion diseases are rare, neurological disorders caused by the misfolding of the cellular prion protein (PrPC). The misfolded conformers aggregate into cytotoxic fibrils (PrPSc) that facilitate the conversion of additional prion proteins into their misfolded form. Intracellular PrPSc aggregates primarily accumulate within late endosomes and lysosomes, organelles that participate in the degradation and turnover of a large subset of the proteome. Thus, intracellular accumulation of PrPSc aggregates have the potential to globally influence protein degradation kinetics. We have analyzed the proteome-wide effect of prion infection on protein degradation rates in N2a neuroblastoma cells by dynamic stable isotopic labeling with amino acids in cell culture (dSILAC) and bottom-up proteomics to quantify the degradation rates of more than 4700 proteins in prion-infected and uninfected cells. As expected, the degradation rate of the prion protein is significantly decreased upon aggregation in infected cells. The data indicate that dilution due to cell division, rather than degradation, is the dominant factor in clearance of PrPSc in infected N2a cells. Conversely, the degradation kinetics of the remainder of the N2a proteome generally increases upon infection. This effect occurs concurrently with increases in the cellular activities of autophagy and lysosomal hydrolases. The resulting enhancement in proteome flux may play a role in the survival of N2a cells during prion infection.
HostingRepository	PRIDE
AnnounceDate	2019-07-26
AnnouncementXML	Submission_2019-07-26_07:43:50.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Charles Hutti
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Fusion Lumos; Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2019-07-11 07:59:11	ID requested
⏵ 1	2019-07-26 07:43:50	announced

Dataset with its publication pending

submitter keyword: cell culture, prion, RML, N2a, lysosome

Sina Ghaemmaghami
contact affiliation	Department of Biologyy, University of Rochester, NY, USA University of Rochester Mass Spectrometry Resource Laboratory, NY, USA
contact email	sghaemma@bio.rochester.edu
lab head
Charles Hutti
contact affiliation	University of Rochester
contact email	chutti@ur.rochester.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/2019/07/PXD014577

PRIDE project URI

• PRIDE
  1. PXD014577
     1. Label: PRIDE project
     2. Name: Global analysis of protein degradation rates during prion infection