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

NCMLS, Department of Molecular Biology, 191, Radboud University of Nijmegen, P.O. Box 9101, 6500 HB Nijmegen, The Netherlands.
Molecular and Cellular Biology (Impact Factor: 5.04). 05/2006; 26(7):2728-35. DOI: 10.1128/MCB.26.7.2728-2735.2006
Source: PubMed

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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Available from: Dimitra J Mitsiou, Jul 07, 2015
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    • "Our study suggests that Taspase1-mediated proteolytic cleavage of TFIIAa-b could serve to interconnect and fine-tune the general and tissuespecific transcription. In somatic cells, precursor TFIIAa-b binds TBP and is functionally active in transcription (Zhou et al., 2006). Therefore, in this context the cleavage of TFIIAa-b may serve to fine-tune the rate of transcription through regulating its stability, as processed TFIIAa/b is known to be more susceptible to degradation (Høiby et al., 2004). "
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