RRC ID 68496
著者 Miyata Y, Yahara I.
タイトル p53-independent association between SV40 large T antigen and the major cytosolic heat shock protein, HSP90.
ジャーナル Oncogene
Abstract The simian double strand DNA tumor virus SV40 encodes the 90-kDa multi-functional protein, large T antigen (LT). LT functions by binding to DNA, as well as to many cellular target proteins such as p53 and retinoblastoma protein (pRB). We report here the identification of a cellular heat shock protein, HSP90, as a previously undescribed LT-associated protein. Immunoprecipitates by anti-HSP90 antibodies from LT-expressing cell lysates contained LT protein, as revealed by Western blotting. Conversely, anti-LT antibody co-immunoprecipitated HSP90. Co-immunoprecipitation of HSP90 and LT was observed even after complete immuno-depletion of p53, indicating that the association of LT with HSP90 is p53-independent. LT-HSP90 complexes can be reconstituted from purified HSP90 and unfolded-LT in vitro in an ATP-independent manner but not from HSP90 and native LT, suggesting that non-mature conformation of LT is required for the efficient association with HSP90. Moreover, geldanamycin, an anti-tumor drug that specifically binds and inhibits HSP90, reduced the intracellular concentration of LT by destabilizing newly synthesized LT. The above results suggest that HSP90 associates with immature forms of LT both in vivo and in vitro, and thus might assist LT in the formation of a functional, mature structure.
巻・号 19(11)
ページ 1477-84
公開日 2000-3-9
DOI 10.1038/sj.onc.1203475
PMID 10723140
MeSH Animals Antibody Specificity Antigens, Viral, Tumor / chemistry Antigens, Viral, Tumor / immunology Antigens, Viral, Tumor / metabolism* Benzoquinones Binding Sites, Antibody COS Cells Cytosol / metabolism* HSP90 Heat-Shock Proteins / antagonists & inhibitors HSP90 Heat-Shock Proteins / immunology HSP90 Heat-Shock Proteins / metabolism* HeLa Cells Humans Immune Sera / metabolism Intracellular Fluid / drug effects Intracellular Fluid / metabolism Lactams, Macrocyclic Precipitin Tests Protein Folding Quinones / pharmacology Rats Simian virus 40 / immunology* Tumor Suppressor Protein p53 / physiology*
IF 7.971
リソース情報
ヒト・動物細胞 A640-3Y1 dl884-3Y1 PAb419(RCB0195)