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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
46
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pubmed:dateCreated |
2001-11-12
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pubmed:abstractText |
Lithium affects several enzymatic activities, however, the molecular mechanisms of lithium actions are not fully understood. We previously showed that LiCl interacts synergistically with all-trans-retinoic acid to promote terminal differentiation of WEHI-3B D(+) cells, a phenomenon accompanied by the recovery of the retinoid-induced loss of retinoic acid receptor alpha protein pools. Here, we demonstrate the effects of LiCl on proteasome-dependent degradation of retinoic acid receptor alpha proteins. LiCl alone, or in combination with all-trans-retinoic acid, increased cellular levels of ubiquitinated retinoic acid receptor alpha and markedly reduced chymotryptic-like activity of WEHI-3B D(+) 20 S and 26 S proteasome enzymes. Neither KCl nor all-trans-retinoic acid affected enzyme activity, whereas NaCl produced a modest reduction at relatively high concentrations. In addition, LiCl inhibited 20 S proteasome chymotryptic-like activity from rabbits but had no effect on tryptic-like activity of the 26 S proteasome. This effect has significant consequences in stabilizing the retinoic acid receptor alpha protein levels that are necessary to promote continued differentiation of leukemia cells in response to all-trans-retinoic acid. In support of this concept, combination of proteasome inhibitors beta-clastolactacystin or benzyloxycarbonyl-Leu-Leu-Phe with all-trans-retinoic acid increased differentiation of WEHI-3B D(+) cells in a manner that was analogous to the combination of LiCl and all-trans-retinoic acid.
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pubmed:grant |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/ATP dependent 26S protease,
http://linkedlifedata.com/resource/pubmed/chemical/Adjuvants, Immunologic,
http://linkedlifedata.com/resource/pubmed/chemical/Chymotrypsin,
http://linkedlifedata.com/resource/pubmed/chemical/Cysteine Endopeptidases,
http://linkedlifedata.com/resource/pubmed/chemical/Lactones,
http://linkedlifedata.com/resource/pubmed/chemical/Lithium Chloride,
http://linkedlifedata.com/resource/pubmed/chemical/Multienzyme Complexes,
http://linkedlifedata.com/resource/pubmed/chemical/Oligopeptides,
http://linkedlifedata.com/resource/pubmed/chemical/Peptide Hydrolases,
http://linkedlifedata.com/resource/pubmed/chemical/Proteasome Endopeptidase Complex,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Retinoic Acid,
http://linkedlifedata.com/resource/pubmed/chemical/Tretinoin,
http://linkedlifedata.com/resource/pubmed/chemical/Trypsin,
http://linkedlifedata.com/resource/pubmed/chemical/Ubiquitin,
http://linkedlifedata.com/resource/pubmed/chemical/clasto-lactacystin beta-lactone,
http://linkedlifedata.com/resource/pubmed/chemical/retinoic acid receptor alpha
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pubmed:status |
MEDLINE
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pubmed:month |
Nov
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pubmed:issn |
0021-9258
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
16
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pubmed:volume |
276
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
42722-7
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pubmed:dateRevised |
2007-11-14
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pubmed:meshHeading |
pubmed-meshheading:11555654-Adjuvants, Immunologic,
pubmed-meshheading:11555654-Animals,
pubmed-meshheading:11555654-Blotting, Western,
pubmed-meshheading:11555654-Cell Differentiation,
pubmed-meshheading:11555654-Cell Line,
pubmed-meshheading:11555654-Chymotrypsin,
pubmed-meshheading:11555654-Cysteine Endopeptidases,
pubmed-meshheading:11555654-Humans,
pubmed-meshheading:11555654-Kinetics,
pubmed-meshheading:11555654-Lactones,
pubmed-meshheading:11555654-Leukemia,
pubmed-meshheading:11555654-Lithium Chloride,
pubmed-meshheading:11555654-Multienzyme Complexes,
pubmed-meshheading:11555654-Oligopeptides,
pubmed-meshheading:11555654-Peptide Hydrolases,
pubmed-meshheading:11555654-Precipitin Tests,
pubmed-meshheading:11555654-Proteasome Endopeptidase Complex,
pubmed-meshheading:11555654-Protein Binding,
pubmed-meshheading:11555654-Protein Biosynthesis,
pubmed-meshheading:11555654-Rabbits,
pubmed-meshheading:11555654-Receptors, Retinoic Acid,
pubmed-meshheading:11555654-Time Factors,
pubmed-meshheading:11555654-Tretinoin,
pubmed-meshheading:11555654-Trypsin,
pubmed-meshheading:11555654-Tumor Cells, Cultured,
pubmed-meshheading:11555654-Ubiquitin
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pubmed:year |
2001
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pubmed:articleTitle |
Inhibition of 20 S and 26 S proteasome activity by lithium chloride: impact on the differentiation of leukemia cells by all-trans retinoic acid.
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pubmed:affiliation |
Department of Pharmacology and Developmental Therapeutics Program, Cancer Center, Yale University School of Medicine, New Haven, Connecticut 06520, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.
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