PXD055366

PXD055366 is an original dataset announced via ProteomeXchange.

Title	HBV remodels PP2A complexes to rewire kinase signaling in hepatocellular carcinoma
Description	Hepatitis B virus (HBV) infection promotes liver cancer initiation by inducing inflammation and cellular stress, but its impact in established tumors is not well understood. We used affinity purification mass spectrometry to comprehensively map a network of 145 physical interactions between HBV and human proteins in hepatocellular carcinoma (HCC). A subset of the host factors targeted by HBV proteins are preferentially mutated in non-HB¬V-associated HCC suggesting that their interaction with HBV influences HCC biology. These include proteins involved in mRNA splicing, mitogenic signaling and DNA repair, with the latter set interacting with the HBV oncoprotein X (HBx). We show that HBx remodels the PP2A phosphatase complex by excluding striatin regulatory subunits from the PP2A holoenzyme. We find that HBx effects on PP2A cause Hippo kinase activation, particularly in cells with high striatin levels. In parallel, HBx activates mTOR complex 2 (mTORC2) to prevent YAP degradation. mTORC2 effects on YAP can be observed in human HCC specimens and mouse HCC models and can be targeted with mTOR kinase inhibitors. Thus, HBV interaction with host proteins rewires HCC signaling rather than directly activating mitogenic pathways. These findings provide a new paradigm for the cellular effects of a tumor promoting virus and support a model where HBV may have therapeutic actionable effects on HCC biology.
HostingRepository	PRIDE
AnnounceDate	2024-11-23
AnnouncementXML	Submission_2024-11-23_12:40:10.088.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	John Gordan
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	phosphorylated residue
Instrument	LTQ Orbitrap Velos; Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2024-08-29 13:23:58	ID requested
⏵ 1	2024-11-23 12:40:10	announced

Dataset with its publication pending

submitter keyword: hepatitis B, PP2A, signaling,hepatocellular carcinoma

John Gordan
contact affiliation	UC San Francisco
contact email	john.gordan@ucsf.edu
lab head
John Gordan
contact affiliation	University of California, San Francisco
contact email	john.gordan@ucsf.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD055366
     1. Label: PRIDE project
     2. Name: HBV remodels PP2A complexes to rewire kinase signaling in hepatocellular carcinoma