RAP80, a nuclear protein with two functional ubiquitin-interaction motifs (UIMs) 
at its N-terminus, plays a critical role in the regulation of estrogen receptor 
alpha and DNA damage response signaling. A yeast two-hybrid screen identified 
the SUMO-conjugating enzyme UBC9 as a protein interacting with RAP80. The 
interaction of RAP80 with UBC9 was confirmed by co-immunoprecipitation and GST 
pull-down analyses. The region between aa 122-204 was critical for the 
interaction of RAP80 with UBC9. In addition, we demonstrate that RAP80 is a 
target for SUMO-1 modification in intact cells. Expression of UBC9 enhanced 
RAP80 mono-sumoylation and also induced multi-sumoylation of RAP80. In addition 
to SUMO-1, RAP80 was efficiently conjugated to SUMO-3 but was only a weak 
substrate for SUMO-2 conjugation. These findings suggest that sumoylation plays 
a role in the regulation of RAP80 functions.