DEVELOPMENT OF PROTEASOME ADAPTORS TO CATALYTICALLY DEPLETE SPECIFIC PROTEINS FROM CELLS


Year of Award:
2016
Award Type:
R21
Project Number:
1R21CA196456-01A1
RFA Number:
RFA-CA-15-002
Technology Track:
Molecular & Cellular Analysis Technologies
PI/Project Leader:
MATOUSCHEK, ANDREAS
Other PI or Project Leader:
Not Applicable
Institution:
UNIVERSITY OF TEXAS, AUSTIN
To develop a novel strategy for depleting cancer-associated proteins from cells that exploits the proteasome-degradation mechanism in cells but side-steps ubiquitination. It is based on bifunctional molecules that will have both a proteasome binding domain as well as a target protein binding domain and thus shuttle targets directly to the proteasome. ÿThe shuttle molecules are designed to escape the proteasome themselves and to recycle to continue to act on additional targets. The approach is meant to directly address various shortcomings associated with RNAi-based strategies.