Ribosomal Protein S6 Interacts with the Latency-Associated Nuclear Antigen of Kaposi's Sarcoma-Associated Herpesvirus

被引:18
作者
Chen, Wuguo [1 ]
Dittmer, Dirk P. [1 ]
机构
[1] Univ N Carolina, Ctr AIDS Res, Lineberger Comprehens Canc Ctr, Dept Microbiol & Immunol, Chapel Hill, NC 27599 USA
关键词
MULTICENTRIC CASTLEMANS-DISEASE; PRIMARY EFFUSION LYMPHOMA; CELL-CYCLE ARREST; GENE-EXPRESSION; DNA-SEQUENCES; TERMINAL REPEATS; BINDING PROTEIN; VIRUS; LANA; P53;
D O I
10.1128/JVI.02620-10
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
The latency-associated nuclear antigen (LANA) is central to the maintenance of Kaposi's sarcoma-associated herpesvirus (KSHV) and to the survival of KSHV-carrying tumor cells. In an effort to identify interaction partners of LANA, we purified authentic high-molecular-weight complexes of LANA by conventional chromatography followed by immunoprecipitation from the BC-3 cell line. This is the first analysis of LANA-interacting partners that is not based on forced ectopic expression of LANA. Subsequent tandem mass spectrometry (MS/MS) analysis identified many of the known LANA-interacting proteins. We confirmed LANA's interactions with histones. Three classes of proteins survived our stringent four-step purification procedure (size, heparin, anion, and immunoaffinity chromatography): two heat shock proteins (Hsp70 and Hsp96 precursor), signal recognition particle 72 (SRP72), and 10 different ribosomal proteins. These proteins are likely involved in structural interactions within LANA high-molecular-weight complexes. Here, we show that ribosomal protein S6 (RPS6) interacts with LANA. This interaction is mediated by the N-terminal domain of LANA and does not require DNA or RNA. Depletion of RPS6 from primary effusion lymphoma (PEL) cells dramatically decreases the half-life of full-length LANA. The fact that RPS6 has a well-established nuclear function beyond its role in ribosome assembly suggests that RPS6 (and by extension other ribosomal proteins) contributes to the extraordinary stability of LANA.
引用
收藏
页码:9495 / 9505
页数:11
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