Document Detail


Distinct IkappaB kinase regulation in adult T cell leukemia and HTLV-I-transformed cells.
MedLine Citation:
PMID:  15878527     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Hideyasu Miura; Michiyuki Maeda; Naoki Yamamoto; Shoji Yamaoka
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Experimental cell research     Volume:  308     ISSN:  0014-4827     ISO Abbreviation:  Exp. Cell Res.     Publication Date:  2005 Aug 
Date Detail:
Created Date:  2005-07-11     Completed Date:  2005-08-16     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  0373226     Medline TA:  Exp Cell Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  29-40     Citation Subset:  IM    
Affiliation:
Department of Molecular Virology, Graduate School of Medicine, Tokyo Medical and Dental University, 1-5-45 Bunkyo-ku, Tokyo 113-8519, Japan.
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MeSH Terms
Descriptor/Qualifier:
Arsenites / 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:
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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