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EV71 3C protease induces apoptosis by cleavage of hnRNP A1 to promote apaf-1 translation


Autoři: Mei-Ling Li aff001;  Jing-Yi Lin aff002;  Bo-Shiun Chen aff003;  Kuo-Feng Weng aff003;  Shin-Ru Shih aff003;  Jesse Davila Calderon aff005;  Blanton S. Tolbert aff005;  Gary Brewer aff001
Působiště autorů: Department of Biochemistry and Molecular Biology, Rutgers Robert Wood Johnson Medical School, Piscataway, NJ, United States of America aff001;  Department of Clinical Laboratory Sciences and Medical Biotechnology, College of Medicine, National Taiwan University, Taipei, Taiwan aff002;  Research Center for Emerging Viral Infections, Chang Gung University, Tao-Yuan, Taiwan aff003;  Department of Medical Biotechnology and Laboratory Science, Chang Gung University, Tao-Yuan, Taiwan aff004;  Department of Chemistry, Case Western Reserve University, Cleveland, OH, United States of America aff005
Vyšlo v časopise: PLoS ONE 14(9)
Kategorie: Research Article
doi: https://doi.org/10.1371/journal.pone.0221048

Souhrn

Enterovirus 71 (EV71) induces apoptosis to promote viral particle release. Earlier work showed that EV71 utilizes its 3C protease to induce apoptosis in a caspase-3-dependent pathway, though the mechanism is unknown. However, work from Vagner, Holcik and colleagues showed that host protein heterogeneous ribonucleoprotein A1 (hnRNP A1) binds the IRES of cellular apoptotic peptidase activating factor 1 (apaf-1) mRNA to repress its translation. In this work, we show that apaf-1 expression is essential for EV71-induced apoptosis. EV71 infection or ectopic expression of 3C protease cleaves hnRNP A1, which abolishes its binding to the apaf-1 IRES. This allows IRES-dependent synthesis of apaf-1, activation of caspase-3, and apoptosis. Thus, we reveal a novel mechanism that EV71 utilizes for virus release via a 3C protease–hnRNP A1–apaf-1–caspase-3–apoptosis axis.

Klíčová slova:

Biology and life sciences – Cell biology – Cell processes – Cell death – Apoptosis – Microbiology – Virology – Viral replication – Internal ribosome entry site – Biochemistry – Enzymology – Enzymes – Proteases – Proteins – Nucleic acids – RNA – Non-coding RNA – Genetics – Gene expression – Gene regulation – Small interfering RNAs – Protein translation – Molecular biology – Molecular biology techniques – Transfection – DNA construction – Plasmid construction – Research and analysis methods – Precipitation techniques – Immunoprecipitation


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