| Uncleaved TFIIA is a substrate for taspase 1 and active in transcription. | |
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MedLine Citation:
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PMID: 16537915 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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In higher eukaryotes, the large subunit of the general transcription factor TFIIA is encoded by the single TFIIAalphabeta gene and posttranslationally cleaved into alpha and beta subunits. The molecular mechanisms and biological significance of this proteolytic process have remained obscure. Here, we show that TFIIA is a substrate of taspase 1 as reported for the trithorax group mixed-lineage leukemia protein. We demonstrate that recombinant taspase 1 cleaves TFIIA in vitro. Transfected taspase 1 enhances cleavage of TFIIA, and RNA interference knockdown of endogenous taspase 1 diminishes cleavage of TFIIA in vivo. In taspase 1-/- MEF cells, only uncleaved TFIIA is detected. In Xenopus laevis embryos, knockdown of TFIIA results in phenotype and expression defects. Both defects can be rescued by expression of an uncleavable TFIIA mutant. Our study shows that uncleaved TFIIA is transcriptionally active and that cleavage of TFIIA does not serve to render TFIIA competent for transcription. We propose that cleavage fine tunes the transcription regulation of a subset of genes during differentiation and development. |
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Authors:
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Huiqing Zhou; Salvatore Spicuglia; James J-D Hsieh; Dimitra J Mitsiou; Torill Høiby; Gert Jan C Veenstra; Stanley J Korsmeyer; Hendrik G Stunnenberg |
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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: Molecular and cellular biology Volume: 26 ISSN: 0270-7306 ISO Abbreviation: Mol. Cell. Biol. Publication Date: 2006 Apr |
Date Detail:
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Created Date: 2006-03-15 Completed Date: 2006-04-24 Revised Date: 2009-11-18 |
Medline Journal Info:
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Nlm Unique ID: 8109087 Medline TA: Mol Cell Biol Country: United States |
Other Details:
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Languages: eng Pagination: 2728-35 Citation Subset: IM |
Affiliation:
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NCMLS, Department of Molecular Biology, 191, Radboud University of Nijmegen, P.O. Box 9101, 6500 HB Nijmegen, The Netherlands. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Amino Acid Sequence Animals Cell Extracts Cell Nucleus / metabolism Embryo, Nonmammalian / metabolism Endopeptidases / metabolism* Gene Expression Regulation, Developmental Hela Cells Humans Molecular Sequence Data Mutation / genetics Peptide Hydrolases / metabolism Protein Processing, Post-Translational* Recombinant Proteins / metabolism Substrate Specificity Transcription Factor TFIIA / chemistry, metabolism* Transcription, Genetic / genetics* Xenopus |
| Chemical | |
Reg. No./Substance:
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0/Cell Extracts; 0/Recombinant Proteins; 0/Transcription Factor TFIIA; EC 3.4.-/Endopeptidases; EC 3.4.-/Peptide Hydrolases; EC 3.4.22.-/taspase1, human |
| Comments/Corrections | |
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