Document Detail


Uncleaved TFIIA is a substrate for taspase 1 and active in transcription.
MedLine Citation:
PMID:  16537915     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
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:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Molecular and cellular biology     Volume:  26     ISSN:  0270-7306     ISO Abbreviation:  Mol. Cell. Biol.     Publication Date:  2006 Apr 
Date Detail:
Created Date:  2006-03-15     Completed Date:  2006-04-24     Revised Date:  2009-11-18    
Medline Journal Info:
Nlm Unique ID:  8109087     Medline TA:  Mol Cell Biol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2728-35     Citation Subset:  IM    
Affiliation:
NCMLS, Department of Molecular Biology, 191, Radboud University of Nijmegen, P.O. Box 9101, 6500 HB Nijmegen, The Netherlands.
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MeSH Terms
Descriptor/Qualifier:
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:
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
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