Purification of native UAF1 complexes containing USP1 and other
deubiquitinating enzymes. A, Flag-HA-tagged UAF1 was
immunoprecipitated from either HeLa cell extracts or cell extracts prepared
from HeLa cells where the endogenous USP1 protein is stably knocked down by
shRNA. The immunoprecipitate was analyzed by immunoblotting using the
indicated antibodies. B, the immunoprecipitates from A were
analyzed for associated deubiquitinating enzyme activity using ubiquitin-AMC
as a substrate. C, silver stain of the UAF1 complexes. D,
glycerol gradient sedimentation of the UAF1 complexes. Fractions were
separated by SDS-PAGE, and proteins were visualized by silver stain.
Subcomplexes as determined by sedimentation profile are indicated by roman
numerals I-IV. Sedimentation profile of molecular weight markers is indicated.
E, the fractions from C were analyzed by immunoblotting
using the indicated antibodies (upper panels) and for
deubiquitinating enzyme activity using ubiquitin-AMC (lower
panel).