| Distinct IkappaB kinase regulation in adult T cell leukemia and HTLV-I-transformed cells. | |
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MedLine Citation:
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PMID: 15878527 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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We have recently shown constitutive IkappaB kinase (IKK) activation and aberrant p52 expression in adult T cell leukemia (ATL) cells that do not express human T cell leukemia virus type I (HTLV-I) Tax, but the mechanism of IKK activation in these cells has remained unknown. Here, we demonstrate distinct regulation of IKK activity in ATL and HTLV-I-transformed T cells in response to protein synthesis inhibition or arsenite treatment. Protein synthesis inhibition for 4 h by cycloheximide (CHX) barely affects IKK activity in Tax-positive HTLV-I-transformed cells, while it diminishes IKK activity in Tax-negative ATL cells. Treatment of ATL cells with a proteasome inhibitor MG132 prior to protein synthesis inhibition reverses the inhibitory effect of CHX, and MG132 alone greatly enhances IKK activity. In addition, treatment of HTLV-I-transformed cells with arsenite for 1 h results in down-regulation of IKK activity without affecting Tax expression, while 8 h of arsenite treatment does not impair IKK activity in ATL cells. These results indicate that a labile protein sensitive to proteasome-dependent degradation governs IKK activation in ATL cells, and suggest a molecular mechanism of IKK activation in ATL cells distinct from that in HTLV-I-transformed T cells. |
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Authors:
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Hideyasu Miura; Michiyuki Maeda; Naoki Yamamoto; Shoji Yamaoka |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Experimental cell research Volume: 308 ISSN: 0014-4827 ISO Abbreviation: Exp. Cell Res. Publication Date: 2005 Aug |
Date Detail:
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Created Date: 2005-07-11 Completed Date: 2005-08-16 Revised Date: 2009-11-19 |
Medline Journal Info:
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Nlm Unique ID: 0373226 Medline TA: Exp Cell Res Country: United States |
Other Details:
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Languages: eng Pagination: 29-40 Citation Subset: IM |
Affiliation:
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Department of Molecular Virology, Graduate School of Medicine, Tokyo Medical and Dental University, 1-5-45 Bunkyo-ku, Tokyo 113-8519, Japan. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Arsenites
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pharmacology Cell Line, Transformed Cell Line, Tumor Cell Transformation, Viral / drug effects, physiology* Cycloheximide / antagonists & inhibitors, pharmacology Enzyme Inhibitors / pharmacology Human T-lymphotropic virus 1 / physiology Humans I-kappa B Kinase Leukemia-Lymphoma, Adult T-Cell / drug therapy, metabolism* Leupeptins / pharmacology Proteasome Endopeptidase Complex / metabolism Protein Synthesis Inhibitors / pharmacology Protein-Serine-Threonine Kinases / antagonists & inhibitors, biosynthesis, metabolism* T-Lymphocytes / drug effects, metabolism |
| Chemical | |
Reg. No./Substance:
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0/Arsenites; 0/Enzyme Inhibitors; 0/Leupeptins; 0/Protein Synthesis Inhibitors; 133407-82-6/benzyloxycarbonylleucyl-leucyl-leucine aldehyde; 15502-74-6/arsenite; 66-81-9/Cycloheximide; EC 2.7.1.-/IKBKE protein, human; EC 2.7.11.1/Protein-Serine-Threonine Kinases; EC 2.7.11.10/CHUK protein, human; EC 2.7.11.10/I-kappa B Kinase; EC 2.7.11.10/IKBKB protein, human; EC 3.4.25.1/Proteasome Endopeptidase Complex |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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