Article
- The EMBO Journal (2004) 23, 3083 - 3091
- doi:10.1038/sj.emboj.7600304
Published online: 15 July 2004
Subject Categories:
Cleavage and proteasome-mediated degradation of the basal transcription factor TFIIA
Torill Høiby1, Dimitra J Mitsiou1,a, Huiqing Zhou1, Hediye Erdjument-Bromage2, Paul Tempst2 and Hendrik G Stunnenberg1
- NCMLS, Department of Molecular Biology, HB Nijmegen, The Netherlands
- Molecular Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA
Correspondence to:
Hendrik G Stunnenberg, NCMLS, Department of Molecular Biology, 191, PO Box 9101, Geert Grooteplein 30, Nijmegen 6525 GA, The Netherlands. Tel.: +31 24 36 10524; Fax: +31 24 36 10520; E-mail: h.stunnenberg@ncmls.kun.nl
aPresent address: Molecular Endocrinology Programme, Institute of Biological Research and Biotechnology, The National Hellenic Research Foundation, 48Vas. Constantinou Av., Athens 11635, Greece
Received 15 December 2003; Accepted 7 June 2004
Abstract
The transcription factor TFIIA is encoded by two genes, TFIIA
and TFIIA
. In higher eukaryotes, the TFIIA is translated as a precursor and undergoes proteolytic cleavage; the regulation and biological implications of the cleavage have remained elusive. We determined by Edman degradation that the TFIIA subunit starts at Asp 278. We found that a cleavage recognition site (CRS), a string of amino acids QVDG at positions -6 to -3 from Asp 278, is essential for cleavage. Mutations in the CRS that prevent cleavage significantly prolong the half-life of TFIIA. Consistently, the cleaved TFIIA is a substrate for the ubiquitin pathway and proteasome-mediated degradation. We show that mutations in the putative phosphorylation sites of TFIIA greatly affect degradation of the -subunit. We propose that cleavage and subsequent degradation fine-tune the amount of TFIIA in the cell and consequently the level of transcription.
Keywords:
- ALF,
- CRS,
- degradation,
- TFIIA cleavage,
- ubiquitylation
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