title: Kaposi's sarcoma-associated herpesvirus-encoded LANA associates with glucocorticoid receptor and enhances its transcriptional activities.
abstract: Kaposi's sarcoma-associated herpesvirus (KSHV)-encoded latency-associated nuclear antigen (LANA), which interacts with cellular proteins, plays a central role in modification of viral and/or cellular gene expression. Here, we show that LANA associates with glucocorticoid receptor (GR), and that LANA enhances the transcriptional activity of GR. Co-immunoprecipitation revealed a physical interaction between LANA and GR in transiently transfected 293T and HeLa cells. In human B-lymphoma cells, LANA overexpression enhanced GR activity and cell growth suppression following glucocorticoid stimulation. Furthermore, confocal microscopy showed that activated GR was bound to LANA and accumulated in the nucleus, leading to an increase in binding of activated GR to the glucocorticoid response element of target genes. Taken together, KSHV-derived LANA acts as a transcriptional co-activator of GR. Our results might suggest a careful use of glucocorticoids in the treatment of patients with KSHV-related malignancies such as Kaposi's sarcoma, primary effusion lymphoma, and multicentric Castleman disease.
authors.affiliation: Department of Immunology, Graduate School of Pharmaceutical Sciences Hokkaido University, Sapporo 060-0812, Japan.
authors.forename: Sumihito
authors.initials: S
authors.lastname: Togi
authors.affiliation: Department of Immunology, Graduate School of Pharmaceutical Sciences Hokkaido University, Sapporo 060-0812, Japan.
authors.forename: Misa
authors.initials: M
authors.lastname: Nakasuji
authors.affiliation: Department of Immunology, Graduate School of Pharmaceutical Sciences Hokkaido University, Sapporo 060-0812, Japan.
authors.forename: Ryuta
authors.initials: R
authors.lastname: Muromoto
authors.affiliation: Department of Immunology, Graduate School of Pharmaceutical Sciences Hokkaido University, Sapporo 060-0812, Japan.
authors.forename: Osamu
authors.initials: O
authors.lastname: Ikeda
authors.affiliation: Department of Immunology, Graduate School of Pharmaceutical Sciences Hokkaido University, Sapporo 060-0812, Japan.
authors.forename: Kanako
authors.initials: K
authors.lastname: Okabe
authors.affiliation: Department of Immunology, Graduate School of Pharmaceutical Sciences Hokkaido University, Sapporo 060-0812, Japan.
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Kitai
authors.affiliation: Department of Immunology, Graduate School of Pharmaceutical Sciences Hokkaido University, Sapporo 060-0812, Japan.
authors.forename: Shigeyuki
authors.initials: S
authors.lastname: Kon
authors.affiliation: Department of Hematology and Oncology, Graduate School of Medicine, Osaka University, 2-2 Yamada-oka, Suita, Osaka 565-0871, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Oritani
authors.affiliation: Department of Immunology, Graduate School of Pharmaceutical Sciences Hokkaido University, Sapporo 060-0812, Japan. Electronic address: tmatsuda@pharm.hokudai.ac.jp.
authors.forename: Tadashi
authors.initials: T
authors.lastname: Matsuda
mesh_terms: D000956:Antigens, Viral / Q000378:metabolism*; D001402:B-Lymphocytes / Q000378:metabolism / Q000821:virology; D002460:Cell Line; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D004247:DNA / Q000378:metabolism; D006367:HeLa Cells; D019288:Herpesvirus 8, Human / Q000502:physiology*; D054884:Host-Pathogen Interactions; D006801:Humans; D009687:Nuclear Proteins / Q000378:metabolism*; D011965:Receptors, Glucocorticoid / Q000235:genetics / Q000378:metabolism*; D012514:Sarcoma, Kaposi / Q000235:genetics / Q000378:metabolism* / Q000821:virology*; D015533:Transcriptional Activation
chemical_list: D000956:Antigens, Viral; D009687:Nuclear Proteins; D011965:Receptors, Glucocorticoid; C109540:latency-associated nuclear antigen; D004247:DNA
keywords: Cross-talk; GR; KSHV; LANA; Transcription