Uncleaved TFIIA is a substrate for taspase 1 and active in transcription

Molecular and Cellular Biology
Huiqing ZhouHendrik G Stunnenberg

Abstract

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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Citations

May 26, 2010·The Journal of Biological Chemistry·Gianpiero SpedaleW W M Pim Pijnappel
Nov 19, 2010·The Journal of Biological Chemistry·Carolin BierRoland H Stauber
Apr 5, 2011·Genes & Development·Edwin SmithAli Shilatifard
Aug 19, 2007·Molecular and Cellular Biology·Francesca CapotostiWinship Herr
Dec 31, 2008·Molecular and Cellular Biology·Wensheng DengStefan G E Roberts
Aug 13, 2013·The Journal of Clinical Investigation·Shugaku TakedaJames J Hsieh
Jun 15, 2007·Biochimica Et Biophysica Acta·Torill HøibyHendrik G Stunnenberg
Mar 23, 2011·Traffic·Carolin BierRoland H Stauber
Jun 17, 2016·Molecular & Cellular Oncology·Hidetaka NiizumaJames J Hsieh
May 23, 2015·Transcription·Barbora MalecováThomas Oelgeschläger
Nov 2, 2013·Developmental Cell·Toshinao OyamaJames J Hsieh
Feb 11, 2015·The Journal of Clinical Investigation·Shugaku TakedaJames J Hsieh
Oct 4, 2016·Genes to Cells : Devoted to Molecular & Cellular Mechanisms·Momoko IsogaiTaka-Aki Tamura
Oct 11, 2017·Journal of Molecular Cell Biology·Christian SchrenkShirley K Knauer
May 25, 2012·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Carolin BierRoland H Stauber
Nov 19, 2015·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Roland H StauberDésirée Wünsch
Jan 31, 2015·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Désirée WünschRoland H Stauber
Feb 27, 2015·Biological Chemistry·Désirée WünschShirley K Knauer
May 27, 2020·Clinical Epigenetics·Shahid BandayMohammad Altaf
Jun 1, 2012·Cancer Research·David Y ChenJames J Hsieh

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