title: Id1 interacts and stabilizes the Epstein-Barr virus latent membrane protein 1 (LMP1) in nasopharyngeal epithelial cells.
abstract: The EBV-encoded latent membrane protein 1 (LMP1) functions as a constitutive active form of tumor necrosis factor receptor (TNFR) and activates multiple downstream signaling pathways similar to CD40 signaling in a ligand-independent manner. LMP1 expression in EBV-infected cells has been postulated to play an important role in pathogenesis of nasopharyngeal carcinoma. However, variable levels of LMP1 expression were detected in nasopharyngeal carcinoma. At present, the regulation of LMP1 levels in nasopharyngeal carcinoma is poorly understood. Here we show that LMP1 mRNAs are transcribed in an EBV-positive nasopharyngeal carcinoma (NPC) cell line (C666-1) and other EBV-negative nasopharyngeal carcinoma cells stably re-infected with EBV. The protein levels of LMP1 could readily be detected after incubation with proteasome inhibitor, MG132 suggesting that LMP1 protein is rapidly degraded via proteasome-mediated proteolysis. Interestingly, we observed that Id1 overexpression could stabilize LMP1 protein in EBV-infected cells. In contrary, Id1 knockdown significantly reduced LMP1 levels in cells. Co-immunoprecipitation studies revealed that Id1 interacts with LMP1 by binding to the CTAR1 domain of LMP1. N-terminal region of Id1 is required for the interaction with LMP1. Furthermore, binding of Id1 to LMP1 suppressed polyubiquitination of LMP1 and may be involved in stabilization of LMP1 in EBV-infected nasopharyngeal epithelial cells.
authors.affiliation: Department of Anatomy, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam Hong Kong Special Administrative Region.
authors.forename: Pok Man
authors.initials: PM
authors.lastname: Hau
authors.forename: Chi Man
authors.initials: CM
authors.lastname: Tsang
authors.forename: Yim Ling
authors.initials: YL
authors.lastname: Yip
authors.forename: Michael S Y
authors.initials: MS
authors.lastname: Huen
authors.forename: Sai Wah
authors.initials: SW
authors.lastname: Tsao
mesh_terms: D015153:Blotting, Western; D002277:Carcinoma; D002460:Cell Line; D045744:Cell Line, Tumor; D020031:Epstein-Barr Virus Infections / Q000235:genetics / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D057809:HEK293 Cells; D006801:Humans; D047468:Immunoprecipitation; D051798:Inhibitor of Differentiation Protein 1 / Q000235:genetics / Q000378:metabolism*; D000077274:Nasopharyngeal Carcinoma; D009303:Nasopharyngeal Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000821:virology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology; D054875:Ubiquitination; D014763:Viral Matrix Proteins / Q000235:genetics / Q000378:metabolism* / Q000502:physiology
chemical_list: C037662:EBV-associated membrane antigen, Epstein-Barr virus; C497453:ID1 protein, human; D051798:Inhibitor of Differentiation Protein 1; D014763:Viral Matrix Proteins