Kaposi's sarcoma-associated herpesvirus-encoded LANA associates with glucocorticoid receptor and enhances its transcriptional activities
Autor: | Yuichi Kitai, Kanako Okabe, Osamu Ikeda, Misa Nakasuji, Ryuta Muromoto, Shigeyuki Kon, Sumihito Togi, Kenji Oritani, Tadashi Matsuda |
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Jazyk: | angličtina |
Rok vydání: | 2015 |
Předmět: |
Transcriptional Activation
LANA viruses Biophysics KSHV Biology medicine.disease_cause Biochemistry Cell Line Glucocorticoid receptor Receptors Glucocorticoid Cell Line Tumor medicine Humans Nuclear protein Kaposi's sarcoma-associated herpesvirus Receptor Molecular Biology Antigens Viral Sarcoma Kaposi Cell Proliferation Hormone response element B-Lymphocytes virus diseases Nuclear Proteins Cross-talk Cell Biology Transfection DNA biochemical phenomena metabolism and nutrition medicine.disease Molecular biology GR Herpesvirus 8 Human Host-Pathogen Interactions Cancer research Primary effusion lymphoma Transcription Glucocorticoid medicine.drug HeLa Cells |
Zdroj: | Biochemical and biophysical research communications. 463(3):395-400 |
ISSN: | 0006-291X |
Popis: | 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. (C) 2015 Elsevier Inc. All rights reserved. |
Databáze: | OpenAIRE |
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