Identify Cell Cycle-Regulatory Substrates Ubiquitinated by the Apoptosis Inhibitor BRUCE

Type of Award: Catalyst
Award Number:
Award Period: July 2011 - June 2013
Amount Awarded: $ 200,000.00
PI(s): Jun Yin, PhD, UChicago; Hiroaki Kiyokawa, MD, PhD, Northwestern University;

Abstract: BRUCE is a member of the IAP (Inhibitors of Apoptosis Proteins) family, which can suppress programmed cell death (apoptosis). Recently BRUCE has also been found to participate in the assembly of a super cellular structure called midbody ring and regulate the proper change of cell shape during cell division. It is still a mystery how BRUCE combines and coordinates these diverse functions in a single protein at different stages of the cell cycle. Much of the interpretation of BRUCE's function is based on its C-terminal E2 domain that mediates the transfer of ubiquitin (Ub) to other cellular proteins. Ub attachment to proteins triggers their degradation thus BRUCE may be a key regulator of the life span of other proteins in the cell. Our goal in this application is to systematically identify the ubiquitination targets of BRUCE in order to elucidate how BRUCE regulates cell division and cell death.