Microsporidian EnP1 alters host cell H2B monoubiquitination and prevents ferroptosis facilitating microsporidia survival

• 成果类型: Article
• 署名作者: Guan, Jingyu; Tang, Liyuan; Wang, Yongliang; Fu, Ming; Xia, Tian; Zheng, Kai; Sabi, Musa Makongoro; Cong, Hua; Wang, Juncheng; Zhou, Chunxue; Zhou, Huaiyu; Weiss, Louis M.; Qu, Hongnan; Han, Bing
• 署名单位: Shandong University; Shandong University; Yeshiva University
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-14649
• DOI: 10.1073/pnas.2400657121
• 发表日期: 2024-08-13
• 关键词: h3 methylation; apoptosis; metabolism; death; ubiquitination; EVOLUTION; proteins; biology

摘要

Microsporidia are intracellular eukaryotic pathogens that pose a substantial threat to immunocompromised hosts. The way these pathogens manipulate host cells during infection remains poorly understood. Using a proximity biotinylation strategy we established that microsporidian EnP1 is a nucleus-targeted effector that modifies the host cell environment. EnP1's translocation to the host nucleus is meditated by nuclear localization signals (NLSs). In the nucleus, EnP1 interacts with host histone H2B. This interaction disrupts H2B monoubiquitination (H2Bub), subsequently impacting p53 expression. Crucially, this inhibition of p53 weakens its control over the downstream target gene SLC7A11, enhancing the host cell's resilience against ferroptosis during microsporidian infection. This favorable condition promotes the proliferation of microsporidia within the host cell. These findings shed light on the molecular mechanisms by which microsporidia modify their host cells to facilitate their survival.