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 transcripti onally active A subunit and two small regulatory B and C subunits, whi ch bind stably to each other to form a binary complex that interacts w ith elongin A and strongly induces its transcriptional activity. The e longin (SIII) complex is a potential target for negative regulation by the von Hippel-Lindau (VHL) tumor suppressor protein, which is capabl e of binding stably to the elongin BC complex and preventing it from a ctivating elongin A, Here, we identify an elongin A domain sufficient for activation of elongation and demonstrate that it is a novel type o f inducible activator that targets the RNA polymerase II elongation co mplex and is evolutionarily conserved in species as distantly related as Caenorhabditis elegans and man, In addition, we demonstrate that bo th the elongin A elongation activation domain and the VHL tumor suppre ssor protein interact with the elongin BC complex through a conserved elongin BC binding site motif that is essential for induction of elong in A activity by elongin BC and for tumor suppression by the VHL prote in.