The inducible elongin A elongation activation domain: structure, function and interaction with the elongin BC complex.
The elongin (SIII) complex strongly stimulates the rate of elongation by RNA polymerase II by suppressing transient pausing by polymerase at many sites along the DNA. Elongin (SIII) is composed of a transcriptionally active A subunit and two small regulatory B and C subunits, which bind stably to each other to form a binary complex that interacts with elongin A and strongly induces its transcriptional activity. The elongin (SIII) complex is a potential target for negative regulation by the von Hippel-Lindau (VHL) tumor suppressor protein, which is capable of binding stably to the elongin BC complex and preventing it from activating elongin A. Here, we identify an elongin A domain sufficient for activation of elongation and demonstrate that it is a novel type of inducible activator that targets the RNA polymerase II elongation complex and is evolutionarily conserved in species as distantly related as Caenorhabditis elegans and man. In addition, we demonstrate that both the elongin A elongation activation domain and the VHL tumor suppressor protein interact with the elongin BC complex through a conserved elongin BC binding site motif that is essential for induction of elongin A activity by elongin BC and for tumor suppression by the VHL protein.
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Program in Molecular and Cell Biology, Oklahoma Medical Research Foundation, Oklahoma City 73104, USA.
Haque
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Barstead
R J
RJ
Conaway
R C
RC
Conaway
J W
JW
D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D017173:Caenorhabditis elegans; D029742:Caenorhabditis elegans Proteins; D017124:Conserved Sequence; D004247:DNA / Q000378:metabolism; D000075065:Elongin; D016147:Genes, Tumor Suppressor; D015698:Genomic Library; D008025:Ligases; D008969:Molecular Sequence Data; D011487:Protein Conformation; D011506:Proteins / Q000378:metabolism; D012319:RNA Polymerase II / Q000378:metabolism; D051381:Rats; D012984:Software; D014157:Transcription Factors / Q000737:chemistry*; D025521:Tumor Suppressor Proteins; D044767:Ubiquitin-Protein Ligases; D051794:Von Hippel-Lindau Tumor Suppressor Protein
D029742:Caenorhabditis elegans Proteins; C000616404:Eloa protein, rat; D000075065:Elongin; D011506:Proteins; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; C000616412:tceb-3 protein, C elegans; D004247:DNA; D044767:Ubiquitin-Protein Ligases; D051794:Von Hippel-Lindau Tumor Suppressor Protein; D012319:RNA Polymerase II; D008025:Ligases