HSP90 is crucial for regulation of LAT expression in activated T cells.
T cell response initiated by engagement of T cell receptor (TCR) is dependent on signal transduction events composed of protein kinases and adaptor proteins. However, the molecular mechanism for gene expression of these proteins is not entirely understood. Here we identified Heat Shock Protein 90 (HSP90) as an essential regulator for gene expression of Linker for activation of T cells (LAT) in primarily activated human T cells. Primarily activated T cells continuously synthesized LAT protein and treatment of cells with 17-AAG, a pharmacological inhibitor of HSP90, decreased LAT protein level following reduction of LAT mRNA. Furthermore, promoter activity of LAT gene was dramatically inhibited by 17-AAG. These results reveal a novel role of HSP90 as a positive regulator for expression of LAT gene in activated T cells.
Department of Pharmacology, Dokkyo Medical University School of Medicine, 880 Kitakobayashi, Mibu, Tochigi 321-0293, Japan. khayashi@dokkyomed.ac.jp
Keitaro
K
Hayashi
Yuichiro
Y
Kamikawa
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics* / Q000378:metabolism; D016227:Benzoquinones / Q000494:pharmacology; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D018841:HSP90 Heat-Shock Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D006801:Humans; D019169:Jurkat Cells; D047029:Lactams, Macrocyclic / Q000494:pharmacology; D007976:Leupeptins / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology*; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000235:genetics; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D061988:Proteasome Inhibitors; D021381:Protein Transport / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology*
D048868:Adaptor Proteins, Signal Transducing; D016227:Benzoquinones; D004791:Enzyme Inhibitors; D018841:HSP90 Heat-Shock Proteins; C112969:HSP90AA1 protein, human; C110810:LAT protein, human; D047029:Lactams, Macrocyclic; D007976:Leupeptins; D008565:Membrane Proteins; D061988:Proteasome Inhibitors; D012333:RNA, Messenger; C112765:tanespimycin; D046988:Proteasome Endopeptidase Complex; C072553:benzyloxycarbonylleucyl-leucyl-leucine aldehyde