Phosphoproteomic Profiling Reveals Epstein-Barr Virus Protein Kinase Integration of DNA Damage Response and Mitotic Signaling

ABSTRACT: Epstein-Barr virus (EBV) is etiologically linked to infectious mononucleosis and several human cancers. EBV encodes a conserved protein kinase BGLF4 that plays a key role in the viral life cycle. To provide new insight into the host proteins regulated by BGLF4, we utilized SILAC-based quantitative proteomics to compare site-specific phosphorylation in BGLF4-expressing cells and found up-regulated phosphorylation of 3,046 unique sites on 1,328 proteins. Motif analysis of the upregulated phospho-proteins found enrichment in CDK1/BGLF4, ATM, ATR and Aurora kinase substrates while functional analyses revealed significant enrichment of pathways related to the DNA damage response, mitosis and cell cycle plus phosphorylation of nuclear pore proteins. Phosphorylation of proteins associated with the mitotic spindle assembly checkpoint (SAC) indicated checkpoint activation, an event that inactivates the anaphase promoting complex/cyclosome, APC/C. Our data reveal that manipulation of mitotic kinase signaling and SAC activation are mechanisms associated with lytic EBV replication.

INSTRUMENT(S): LTQ Orbitrap Velos, LTQ Orbitrap Elite

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): B Cell

SUBMITTER: Renfeng Li  

LAB HEAD: Renfeng Li

PROVIDER: PXD002411 | Pride | 2015-12-07

REPOSITORIES: Pride