PXD012767

PXD012767 is an original dataset announced via ProteomeXchange.

Title	HCV Hypo- vs. Hyper-Phosphorylated NS5A Interactome
Description	Chronic hepatitis C virus (HCV) infection is a leading cause of liver cancer. HCV propagation and oncogenicity depend in part on the phosphorylation states of its non-structural protein 5A (NS5A); however, little is known about how hypo- or hyper-phosphorylated NS5A functions. Here, we segregated hypo- from hyper-phosphorylated NS5A in HCV-infected Huh7.5.1 cells with two custom-made specific antibodies and differentiated their interacting proteins with dimethyl labeling-based quantitative proteomics. Bioinformatics analysis revealed that hyper-phosphorylated NS5A preferentially binds the polymerase II-associated factor 1 complex known to alter host gene expression involved in cancer progression. In contrast, hypo-phosphorylated NS5A binds proteins involved in host antiviral response. Moreover, we found that the hypo-phosphorylated NS5A binds DNA-dependent protein kinase catalytic subunit (DNA-PKcs) predicted to phosphorylate NS5A at serine 232, a key amino acid that governs NS5A transition from hypo- to hyper-phosphorylation state. Inhibition of DNA-PKcs with an inhibitor or via gene-specific knockdown significantly reduced serine 232 phosphorylation and NS5A hyper-phosphorylation. Collectively, we have identified a protein kinase that regulates a delicate balance of NS5A between hypo- and hyper-phosphorylation states respectively involved in host antiviral responses and liver cancer progression.
HostingRepository	PRIDE
AnnounceDate	2019-06-17
AnnouncementXML	Submission_2019-06-17_05:21:02.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Ming-Jiun Yu
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	phosphorylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	LTQ Orbitrap Velos

Revision	Datetime	Status	ChangeLog Entry
0	2019-02-18 07:48:13	ID requested
⏵ 1	2019-06-17 05:21:04	announced

Pan TC, Lo CW, Chong WM, Tsai CN, Lee KY, Chen PY, Liao JC, Yu MJ, Differential Proteomics Reveals Discrete Functions of Proteins Interacting with Hypo- versus Hyper-phosphorylated NS5A of the Hepatitis C Virus. J Proteome Res, 18(7):2813-2825(2019) [pubmed]

submitter keyword: HCV, NS5A, liver, cancer, antiviral

Ming-Jiun Yu
contact affiliation	Institute of Biochemistry and Molecular Biology, College of Medicine, National Taiwan University, Taiwan
contact email	mjyu@ntu.edu.tw
lab head
Ming-Jiun Yu
contact affiliation	Institute of Biochemistry and Molecular Biology
contact email	mjyu@ntu.edu.tw
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD012767
     1. Label: PRIDE project
     2. Name: HCV Hypo- vs. Hyper-Phosphorylated NS5A Interactome