title: KSHV LANA and EBV LMP1 induce the expression of UCH-L1 following viral transformation.
abstract: Ubiquitin C-terminal Hydrolase L1 (UCH-L1) has oncogenic properties and is highly expressed during malignancies. We recently documented that Epstein-Barr virus (EBV) infection induces uch-l1 expression. Here we show that Kaposi's Sarcoma-associated herpesvirus (KSHV) infection induced UCH-L1 expression, via cooperation of KSHV Latency-Associated Nuclear Antigen (LANA) and RBP-Jκ and activation of the uch-l1 promoter. UCH-L1 expression was also increased in Primary Effusion Lymphoma (PEL) cells co-infected with KSHV and EBV compared with PEL cells infected only with KSHV, suggesting EBV augments the effect of LANA on uch-l1. EBV latent membrane protein 1 (LMP1) is one of the few EBV products expressed in PEL cells. Results showed that LMP1 was sufficient to induce uch-l1 expression, and co-expression of LMP1 and LANA had an additive effect on uch-l1 expression. These results indicate that viral latency products of both human γ-herpesviruses contribute to uch-l1 expression, which may contribute to the progression of lymphoid malignancies.
authors: Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, USA.
authors: Gretchen L
authors: GL
authors: Bentz
authors: Anjali
authors: A
authors: Bheda-Malge
authors: Ling
authors: L
authors: Wang
authors: Julia
authors: J
authors: Shackelford
authors: Blossom
authors: B
authors: Damania
authors: Joseph S
authors: JS
authors: Pagano
mesh_terms: D000956:Antigens, Viral / Q000235:genetics / Q000378:metabolism*; D002461:Cell Line, Transformed; D002472:Cell Transformation, Viral; D020031:Epstein-Barr Virus Infections / Q000201:enzymology* / Q000235:genetics / Q000821:virology; D006566:Herpesviridae Infections / Q000201:enzymology* / Q000235:genetics / Q000821:virology; D004854:Herpesvirus 4, Human / Q000235:genetics / Q000378:metabolism*; D019288:Herpesvirus 8, Human / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D043222:Ubiquitin Thiolesterase / Q000235:genetics* / Q000378:metabolism; D015854:Up-Regulation; D014763:Viral Matrix Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D000956:Antigens, Viral; C037662:EBV-associated membrane antigen, Epstein-Barr virus; D009687:Nuclear Proteins; C482860:UCHL1 protein, human; D014763:Viral Matrix Proteins; C109540:latency-associated nuclear antigen; D043222:Ubiquitin Thiolesterase
keywords: EBV; KSHV; LANA; LMP1; UCH-L1