Regulatory mimicry of cyclin- dependent kinases by a conserved herpesvirus protein kinase

• 成果类型: Article
• 署名作者: Koyanagi, Naoto; Hengphasatporn, Kowit; Kato, Akihisa; Nobe, Moeka; Takeshima, Kosuke; Maruzuru, Yuhei; Maenaka, Katsumi; Shigeta, Yasuteru; Kawaguchi, Yasushi
• 署名单位: University of Tokyo; University of Tokyo; University of Tokyo; University of Tsukuba; Hokkaido University; Hokkaido University; University of Tokyo
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-14549
• DOI: 10.1073/pnas.2500264122
• 发表日期: 2025-04-22
• 关键词: simplex-virus; tyrosine phosphorylation; retinoblastoma protein; in-vitro; complex; target; cells; yeast; ul97; cdk5

摘要

Herpesviruses encode conserved protein kinases (CHPKs) that target dependent kinase (CDK) phosphorylation sites; thus, they are termed kinases. Tyrosine 15 in the GxGxxG motifs of CDK1 and CDK2, whose tion down-regulates their catalytic activities, is conserved in the corresponding CHPKs. We found that CHPK UL13, the corresponding Tyr-162 in virus 2 (HSV-2), was phosphorylated in HSV-2-infected cells. Mutational HSV-2 UL13 Tyr-162 suggested that phosphorylation of UL13 Tyr-162 phosphorylation of all UL13 substrates tested in HSV-2-infected cells. suggested that HSV-2 UL13 mimicked the regulatory mechanism of CDKs this CHPK has regulatory and functional mimicrywith CDKs. Furthermore, rylation of HSV-2 UL13 Tyr-162 was suggested to be required for the downregulation of viral replication and pathogenicity, specifically in the brains of mice, and viral recurrence in guinea pigs. These findings highlight the dual impact of mimicry of CDKs by CHPK on the fine-tuned regulation of lytic and infections in vivo.