Uncleaved TFIIA is a Substrate for Taspase 1 and Active in Transcription

Overview

Journal Mol Cell Biol

Specialty Cell Biology

Date 2006 Mar 16

PMID 16537915

Citations 43

Authors

Huiqing Zhou

Salvatore Spicuglia

James J-D Hsieh

Dimitra J Mitsiou

Torill Hoiby

Gert Jan C Veenstra

Stanley J Korsmeyer

Hendrik G Stunnenberg

Affiliations

Soon will be listed here.

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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