Mechanisms of degradation of human papillomavirus DNA helicase E1

2017 Fiscal Year Final Research Report

• Project/Area Number: 26460564
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Virology
• Research Institution: National Institute of Infectious Diseases
• Principal Investigator: Kukimoto Iwao 国立感染症研究所, 病原体ゲノム解析研究センター, 室長 (70291127)
• Project Period (FY): 2014-04-01 – 2018-03-31
• Keywords: ヒトパピローマウイルス / 子宮頸癌 / ユビキチン / タンパク質分解

Outline of Final Research Achievements

Genome replication of human papillomavirus requires viral replicative DNA helicase E1, and regulation of intracellular E1 levels is important for controlling the virus life cycle. This study aimed to elucidate viral and cellular mechanisms of regulating E1 levels. We found that E1 was degraded in a manner dependent on its own ATPase activity, and that E1 was poly-ubiquitinated and degraded via the proteasome pathway. We further demonstrated that intracellular E1 levels were up-regulated with the treatment of tankyrase inhibitor XAV939, although the potential target of XAX939 for E1 up-regulation was not tankyrase but poly-ADP-ribose polymerase 1 (PARP1), suggesting that PARP1 is involved in negative regulation of E1 function.

Free Research Field

ウイルス学