Abstract B03: Physical and functional interactions between two tumor suppressors, BIN1 and RB1

The bridging integrator 1 (BIN1) protein was originally identified as a cellular adaptor protein that interacts with the transcription factor c-MYC and inhibits cell proliferation. However, BIN1 inhibits tumor cell growth by both a BIN1 MYC-binding domain (MBD)-dependent mechanism and an MBD-independent mechanism. Consistently, BIN1 promotes skeletal muscle differentiation in vitro where c-MYC is not detectable, suggesting that an undefined BIN1-interacting protein other than c-MYC determines BIN1-mediated growth arrest in an MYC-independent manner.Here we show the functional interplay between BIN1 and the RB1 tumor suppressor for growth arrest. BIN1 interacts with RB1 in differentiated (i.e. growth-arrested) C2C12 skeletal myotube cells, whereas such interaction was largely reduced in undifferentiated (i.e. actively proliferating) C2C12 myoblast cells. Acting through the coiled-coil BAR domain, an essential effector region for BIN1-mediated growth suppression, BIN1 physically interacts with the C pocket domain of RB1 in vitro and in vivo. The RB1-BIN1 protein-protein interaction is functionally germane. First, adenovirus E1A viral oncoprotein, which is known to stimulate cell proliferation in rodent fibroblast model systems by interacting with RB1, disrupted the RB1-BIN1 interaction in vitro. Second, the cancer suppression mediated by overexpressed BIN1 was partly attenuated by the co-transfection of short-hairpin RNA against RB1. Third, an MBD-independent BIN1-associated tr...
Source: Molecular Cancer Research - Category: Cancer & Oncology Authors: Tags: Rb Bench to Bedside: Novel Functions and Clinical Implications: Poster Presentations - Proffered Abstracts Source Type: research