Abstract
Retinoblastoma-binding protein 2 (Rbp2) was originally identified as a retinoblastoma protein (RB) pocket domain-binding protein. Although Rbp2 has been shown to interact with RB, p107, TATA-binding protein, and T-cell oncogene rhombotin-2, the physiological function of Rbp2 remains unclear. Here we demonstrate that Rbp2 not only binds to nuclear receptors (NRs) but also enhances the transcription mediated by them. Rbp2 interacts with the DNA-binding domains of NRs and potentiates NR-mediated transcription in an AF-2-dependent manner. Both the N-terminal and C-terminal domains of Rbp2 are critical 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 coregulator of NRs and define a potential role for Rbp2 in NR-mediated transcription.
Highlights
The retinoblastoma protein (RB)1 plays a pivotal role in the control of cell proliferation, development, and differentiation [1]
To examine the potential association of Retinoblastoma-binding protein 2 (Rbp2) with nuclear receptors (NRs), Estrogen receptor (ER) was fused to Glutathione S-transferase (GST) to generate GST-ER and incubated with 35Slabeled Rbp2 in the presence or absence of 17-estradiol. 35SLabeled Rbp2 was retained on GST-ER beads in a ligandindependent manner (Fig. 1A, lanes 4 and 5) but not on GST or GST-YKT6 beads [40], a protein involved in vesicle transport (Fig. 1A, lanes 3 and 12). 35S-Labeled Rbp2 was retained by the GST-RB pocket (Fig. 1A, lane 13), serving as a positive control
GST fusion proteins containing retinoic acid receptor (RAR), glucocorticoid receptor (GR), and vitamin D receptor (VDR) were produced and tested for interaction with 35S-labeled Rbp2. All these have the ability to retain Rbp2 in the presence and absence of ligands, with different efficiencies (Fig. 1A, lanes 6 –11). These results suggest that Rbp2 may directly interact with NRs in vitro in a ligand-independent manner
Summary
The retinoblastoma protein (RB)1 plays a pivotal role in the control of cell proliferation, development, and differentiation [1]. Rbp2 interacts with the DNA-binding domains of NRs and potentiates NR-mediated transcription in an AF-2-dependent manner.
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