PXD006005

PXD006005 is an original dataset announced via ProteomeXchange.

Title	Quantitative analysis of the proteome response to the histone deacetylase inhibitor (HDACi) Vorniostat in Niemann-Pick Type C1 disease
Description	Niemann-Pick type C (NPC) disease is an inherited, progressive neurodegenerative disorder principally caused by mutations in the NPC1 gene. NPC disease is characterized by the accumulation of unesterified cholesterol in the late endosomes (LE) and lysosomes (LE) (LE/LY). Vorinostat, a histone deacetylase inhibitor (HDACi), restores cholesterol homeostasis in fibroblasts derived from NPC patients; however, the exact mechanism by which Vorinostat restores cholesterol level is not known yet. In this study, we performed comparative proteomic profiling of the response of NPC1-I1061T fibroblasts to Vorinostat. After stringent statistical criteria to filter identified proteins, we observed 202 proteins that are differentially expressed in Vorinostat-treated fibroblasts. These proteins are members of diverse cellular pathways including the endomembrane dependent protein folding-stability-degradation-trafficking axis, energy metabolism, and lipid metabolism. Our study shows that treatment of NPC1-I1061T fibroblasts with Vorinostat not only enhances pathways promoting the folding, stabilization and trafficking of NPC1 (I1061T) mutant to the LE/LY, but alters the expression of lysosomal proteins, specifically the lysosomal acid lipase (LIPA) involved in the LIPA->NPC2->NPC1 based flow of cholesterol from the LE/LY lumen to the LE/LY membrane. We posit that the Vorinostat may modulate numerous pathways that operate in an integrated fashion through epigenetic and post-translational modifications reflecting acetylation/deacetylation balance to help manage the defective NPC1 fold, the function of the LE/LY system and/or additional cholesterol metabolism/distribution pathways, that could globally contribute to improved mitigation of NPC1 disease in the clinic based on as yet uncharacterized principles of cellular metabolism dictating cholesterol homeostasis.
HostingRepository	PRIDE
AnnounceDate	2017-09-11
AnnouncementXML	Submission_2017-09-11_01:55:14.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Navin Rauniyar
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	iodoacetamide derivatized residue
Instrument	LTQ Orbitrap Velos

Revision	Datetime	Status	ChangeLog Entry
0	2017-03-03 02:05:17	ID requested
⏵ 1	2017-09-11 01:55:15	announced

Subramanian K, Rauniyar N, Lavalle, é, -Adam M, Yates JR, Balch WE, Quantitative Analysis of the Proteome Response to the Histone Deacetylase Inhibitor (HDACi) Vorinostat in Niemann-Pick Type C1 disease. Mol Cell Proteomics, 16(11):1938-1957(2017) [pubmed]

ProteomeXchange project tag: Biology/Disease-Driven Human Proteome Project (B/D-HPP), Human Proteome Project

curator keyword: Biological, Biomedical

submitter keyword: Niemann-Pick Type C1 (NPC1) disease NPC1, Tandem Mass Tag, TMT, lysosomal acid lipase, LIPA, proteomics, quantitative proteomics, vorinostat

William E. Balch
contact affiliation	Department of Cell and Molecular Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA-92037
contact email	webalch@scripps.edu
lab head
Navin Rauniyar
contact affiliation	Yale University
contact email	navin.rauniyar@yale.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/2017/09/PXD006005

PRIDE project URI

• PRIDE
  1. PXD006005
     1. Label: PRIDE project
     2. Name: Quantitative analysis of the proteome response to the histone deacetylase inhibitor (HDACi) Vorniostat in Niemann-Pick Type C1 disease