Cleavage and proteasome-mediated degradation of the basal transcription factor TFIIA Journal Article
| Authors: | Høiby, T.; Mitsiou, D. J.; Zhou, H.; Erdjument-Bromage, H.; Tempst, P.; Stunnenberg, H. G. |
| Article Title: | Cleavage and proteasome-mediated degradation of the basal transcription factor TFIIA |
| Abstract: | The transcription factor TFIIA is encoded by two genes, TFIIAαβ and TFIIAγ. In higher eukaryotes, the TFIIAαβ 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 TFIIAβ 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 TFIIAβ greatly affect degradation of the β-subunit. We propose that cleavage and subsequent degradation fine-tune the amount of TFIIA in the cell and consequently the level of transcription. |
| Keywords: | controlled study; protein phosphorylation; unclassified drug; gene mutation; human cell; mutation; ubiquitin; animals; gene; proteasome; proteasome endopeptidase complex; protein degradation; cell line; protein stability; cercopithecus aethiops; transcription factors; amino acid sequence; molecular sequence data; sequence alignment; eukaryota; substrate specificity; binding site; aspartic acid; degradation; ubiquitylation; beta chain; transcription factor iia; humans; human; priority journal; article; transcription factor tfiia; alf; crs; tfiia cleavage; glutaminylvalylaspartylglycine; cleavage recognition site; tfiiaalphabeta gene; tfiiagamma gene |
| Journal Title: | EMBO Journal |
| Volume: | 23 |
| Issue: | 15 |
| ISSN: | 0261-4189 |
| Publisher: | Wiley Blackwell |
| Date Published: | 2004-08-04 |
| Start Page: | 3083 |
| End Page: | 3091 |
| Language: | English |
| DOI: | 10.1038/sj.emboj.7600304 |
| PROVIDER: | scopus |
| PMCID: | PMC514921 |
| PUBMED: | 15257296 |
| DOI/URL: | |
| Notes: | EMBO J. -- Cited By (since 1996):11 -- Export Date: 16 June 2014 -- CODEN: EMJOD -- Source: Scopus |
