Retinoblastoma-binding protein 2 (Rbp2) was originally identified as a reti
noblastoma protein (RB) pocket domain-binding protein. Although Rbp2 has be
en shown to interact with RB, p107, TATA-binding protein, and T-cell oncoge
ne rhombotin-2, the physiological function of Rbp2 remains unclear. Here we
demonstrate that Rbp2 not only binds to nuclear receptors (NRs) but also e
nhances the transcription mediated by them. Rbp2 interacts with the DNA-bin
ding domains of NRs and potentiates NR-mediated transcription in an AF-2-de
pendent manner. Both the N-terminal and C-terminal domains of Rbp2 are crit
ical for the transactivation activity of Rbp2 on NRs. The C terminus is the
NR-interacting region. In addition, RB functions in maximizing the effect
of Rbp2 on the transcription by NRs. These results suggest that Rbp2 is a c
oregulator of NRs and define a potential role for Rbp2 in NR-mediated trans
cription.