Source:http://linkedlifedata.com/resource/pubmed/id/12427542
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
2-3
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pubmed:dateCreated |
2002-11-12
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pubmed:abstractText |
Cystathionine-beta-synthase (CBS) catalyzes the condensation of serine and homocysteine to form cystathionine, an intermediate step in the synthesis of cysteine. We previously described essential transactivating roles for specificity protein 1 (Sp1), Sp3, nuclear factor Y (NF-Y), and USF-1 in the regulation of the CBS-1b promoter. Differential binding of Sp1/Sp3 to the CBS-1b promoter due to differences in Sp1/Sp3 phosphorylation, and Sp1/Sp3 synergism with NF-Y might, in part, explain cell-specific patterns of CBS expression. In this report, the roles of various NF-YA isoforms in influencing cell-specific differences in CBS gene expression were determined in HT1080 and HepG2 cells. Seven unique NF-YA isoforms were detected in HT1080 by reverse transcriptase-PCR (RT-PCR) and DNA sequencing, characterized by deletions in the glutamine-rich and/or serine/threonine-rich domains. Only four of the seven NF-YA isoforms were found in HepG2 cells. The six alternatively spliced NF-YA isoforms all showed significantly less synergistic transactivation of the CBS-1b promoter with Sp1 than wild-type NF-YA, as determined by cotransfections in Drosophila SL2 cells with NF-YB and NF-YC. Further, all six alternatively spliced NF-YA isoforms inhibited the synergistic transactivation of the CBS-1b promoter by wild-type NF-Y and Sp1. Thus, the cellular distributions of these alternatively spliced NF-YA isoforms could impart an important cell-specific component to CBS transcriptional regulation, by virtue of their abilities to directly synergize with Sp1/Sp3 and interfere with transactivation of the CBS-1b promoter by wild-type NF-Y. Characterization of CBS promoter structure and function should clarify the molecular bases for variations in CBS gene expression in genetic diseases and the relationship between CBS and Down's syndrome (DS).
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pubmed:grant | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/CCAAT-Binding Factor,
http://linkedlifedata.com/resource/pubmed/chemical/Cystathionine beta-Synthase,
http://linkedlifedata.com/resource/pubmed/chemical/DNA, Recombinant,
http://linkedlifedata.com/resource/pubmed/chemical/NFYA protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Isoforms,
http://linkedlifedata.com/resource/pubmed/chemical/RNA,
http://linkedlifedata.com/resource/pubmed/chemical/Sp1 Transcription Factor,
http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factors
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pubmed:status |
MEDLINE
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pubmed:month |
Dec
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pubmed:issn |
0006-3002
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:day |
12
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pubmed:volume |
1579
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
73-80
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pubmed:dateRevised |
2008-11-21
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pubmed:meshHeading |
pubmed-meshheading:12427542-Base Sequence,
pubmed-meshheading:12427542-CCAAT-Binding Factor,
pubmed-meshheading:12427542-Cystathionine beta-Synthase,
pubmed-meshheading:12427542-DNA, Recombinant,
pubmed-meshheading:12427542-Drug Synergism,
pubmed-meshheading:12427542-Gene Expression Regulation, Enzymologic,
pubmed-meshheading:12427542-Humans,
pubmed-meshheading:12427542-Promoter Regions, Genetic,
pubmed-meshheading:12427542-Protein Isoforms,
pubmed-meshheading:12427542-RNA,
pubmed-meshheading:12427542-Sp1 Transcription Factor,
pubmed-meshheading:12427542-Transcription Factors,
pubmed-meshheading:12427542-Transcriptional Activation,
pubmed-meshheading:12427542-Tumor Cells, Cultured
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pubmed:year |
2002
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pubmed:articleTitle |
Synergistic regulation of human cystathionine-beta-synthase-1b promoter by transcription factors NF-YA isoforms and Sp1.
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pubmed:affiliation |
Experimental and Clinical Therapeutics Program, Barbara Ann Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, MI, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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