Identifying novel substrates of Epstein-Barr virus-encoded protein kinase (EBV-PK)

2019 Fiscal Year Final Research Report

• Project/Area Number: 19K21264
• Project/Area Number (Other): 18H06151 (2018)
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund (2019); Single-year Grants (2018)
• Review Section: 0803:Pathology, infection/immunology, and related fields
• Research Institution: Fujita Health University
• Principal Investigator: IWAHORI SATOKO 藤田医科大学, 医学部, 講師 (80416164)
• Project Period (FY): 2018-08-24 – 2020-03-31
• Keywords: EBウイルス / キナーゼ / リン酸化 / 蛋白質分解 / MTA1 / SF3B1

Outline of Final Research Achievements

Epstein-Barr virus (EBV) is a human lymphotropic herpesvirus, which is causally associated with infectious mononucleosis as well as a variety of human cancers. The EBV-encoded protein kinase (EBV-PK) is a Ser/Thr protein kinase and a functional ortholog of cyclin-dependent kinases (CDKs), termed a viral CDK (v-CDK). In this study, metastasis-associated protein 1 (MTA1) and splicing factor 3B subunit 1 (SF3B1) were identified as novel EBV-PK substrates. Phosphorylation of MTA1 by EBV-PK induced degradation of MTA1 and this degradation was dependent on ubiquitin-proteasome pathways. The phosphorylation-dependent degradation of MTA1 might be a conserved function of cellular CDKs and could explain MTA1 levels during cancer metastasis. In the case of SF3B1, human cytomegalovirus v-CDK (UL97) as well as EBV-PK was shown to phosphorylate it. Whether phosphorylation affects the function of SF3B1 is under investigation.

Free Research Field

ウイルス学

Academic Significance and Societal Importance of the Research Achievements

EBV-PKによるリン酸化を細胞内の他のキナーゼによるリン酸化と区別する方法（chemical genetics approach）を開発し、質量分析法によりEBV-PKの直接的な標的因子として21因子（うち2つの既知標的因子を含む）を同定し、MTA1とSF3B1について特に解析した。EBV-PKは細胞由来cyclin-dependent kinase(CDK)の機能ホモログであり、本研究の成果はウイルス学に限らず、一般細胞生物学にも貢献することが期待できる。