CHARACTERIZATION OF ELONGIN-C FUNCTIONAL DOMAINS REQUIRED FOR INTERACTION WITH ELONGIN-B AND ACTIVATION OF ELONGIN-A

The Elongin (SIII) complex stimulates the rate of elongation by RNA po lymerase II by suppressing transient pausing by polymerase at many sit es along DNA templates. The Elongin (SIII) complex is composed of a tr anscriptionally active A subunit, a chaperone-like B subunit, which pr omotes assembly and enhances stability of the Elongin (SIII) complex, and a regulatory C subunit, which (i) functions as a potent activator of Elongin A transcriptional activity, (ii) interacts specifically wit h Elongin B to form an isolable Elongin BC complex, and (iii) is bound and negatively regulated in vitro by the product of the von Hippel-Li ndau tumor suppressor gene. As part of our effort to understand how El ongin C regulates the activity of the Elongin (SIII) complex, we are c haracterizing Elongin C functional domains. In this report, we identif y Elongin C mutants that fall into multiple functional classes based o n their abilities to bind Elongin B and to bind and activate Elongin A under our assay conditions. Characterization of these mutants suggest s that Elongin C is composed of multiple overlapping regions that medi ate functional interactions with Elongin A and B.