title: Caspase-dependent cleavage regulates protein levels of Epstein-Barr virus-derived latent membrane protein 1.
abstract: Epstein-Barr virus (EBV)-encoded latent membrane protein-1 (LMP1) plays pathogenic roles in EBV-related diseases. Thus, host cells employ several mechanisms to regulate LMP1 functions, and we previously reported possible regulation by signal transducing adaptor protein-2 as well as BS69. Here, we found that caspase-3 mainly degraded LMP1 proteins in HeLa cells, leading to decreased NF-κB and STAT3 activation. Caspase-3 cleaved the consensus DNTD sequences in the CTAR3 region of LMP1. Of importance, LMP1 expression strongly enhanced caspase-3 activity. Taken together, the reduction of LMP1 protein levels by caspases is likely to be a newly identified host defense against EBV infection.
authors.affiliation: Department of Immunology, Graduate School of Pharmaceutical Sciences, Hokkaido University, Kita-Ku, Sapporo, Japan.
authors.forename: Sumihito
authors.initials: S
authors.lastname: Togi
authors.affiliation: Department of Immunology, Graduate School of Pharmaceutical Sciences, Hokkaido University, Kita-Ku, Sapporo, Japan.
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Hatano
authors.affiliation: Department of Immunology, Graduate School of Pharmaceutical Sciences, Hokkaido University, Kita-Ku, Sapporo, Japan.
authors.forename: Ryuta
authors.initials: R
authors.lastname: Muromoto
authors.affiliation: Department of Immunology, Graduate School of Pharmaceutical Sciences, Hokkaido University, Kita-Ku, Sapporo, Japan.
authors.forename: Eri
authors.initials: E
authors.lastname: Kawanishi
authors.affiliation: Department of Immunology, Graduate School of Pharmaceutical Sciences, Hokkaido University, Kita-Ku, Sapporo, Japan.
authors.forename: Osamu
authors.initials: O
authors.lastname: Ikeda
authors.affiliation: Department of Immunology, Graduate School of Pharmaceutical Sciences, Hokkaido University, Kita-Ku, Sapporo, Japan.
authors.forename: Koki
authors.initials: K
authors.lastname: Hirashima
authors.affiliation: Department of Immunology, Graduate School of Pharmaceutical Sciences, Hokkaido University, Kita-Ku, Sapporo, Japan.
authors.forename: Shigeyuki
authors.initials: S
authors.lastname: Kon
authors.affiliation: Department of Immunology, Graduate School of Pharmaceutical Sciences, Hokkaido University, Kita-Ku, Sapporo, Japan.
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Kitai
authors.affiliation: Department of Molecular Immunology, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka, Japan.
authors.forename: Teruhito
authors.initials: T
authors.lastname: Yasui
authors.affiliation: Department of Hematology and Oncology, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Oritani
authors.affiliation: Department of Immunology, Graduate School of Pharmaceutical Sciences, Hokkaido University, Kita-Ku, Sapporo, Japan.
authors.forename: Tadashi
authors.initials: T
authors.lastname: Matsuda
mesh_terms: D053148:Caspase 3 / Q000235:genetics / Q000378:metabolism*; D061945:Caspase Inhibitors / Q000494:pharmacology; D004789:Enzyme Activation; D015870:Gene Expression; D005814:Genes, Viral; D006367:HeLa Cells; D004854:Herpesvirus 4, Human / Q000235:genetics / Q000472:pathogenicity / Q000502:physiology; D054884:Host-Pathogen Interactions; D006801:Humans; D016328:NF-kappa B / Q000378:metabolism; D009842:Oligopeptides / Q000494:pharmacology; D017434:Protein Structure, Tertiary; D059748:Proteolysis; D034741:RNA, Small Interfering / Q000235:genetics; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000378:metabolism; D014763:Viral Matrix Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
chemical_list: D061945:Caspase Inhibitors; C037662:EBV-associated membrane antigen, Epstein-Barr virus; D016328:NF-kappa B; D009842:Oligopeptides; D034741:RNA, Small Interfering; D011994:Recombinant Proteins; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D014763:Viral Matrix Proteins; C517629:benzyloxycarbonyl-valyl-alanyl-aspartic acid; C505407:CASP3 protein, human; D053148:Caspase 3
keywords: EBV; LMP1; NF-κB activation; caspase; degradation