UC San Diego

Retinoblastom protein, lacking in any catalytic domain, is a scaffolding protein. It functions through bringing protein complexes together and has been shown to regulate cells processes such as cell cycle progression and programmed cell death, apoptosis. Regulation of RB and its binding partners occurs in a variety of ways. In the E2F transcription factor case, RB is hyperphosphorylated to induce intra-domain interaction thus releasing E2F. Other avenues to regulating RB includes the process of TNF induced apoptosis which proceeds with a specific caspase cleavage of the last 42 amino acids of RB. By applying mass spectrometry and a number of in vitro binding assays, we have identified several proteins that interact with the C-terminal region of RB. Our results demonstrate that survivin and [Beta]-catenin interact with the C-terminal portion of RB. Nonmuscle Myosin Heavy Chain II A has been shown to specifically interact with the terminal 42 amino acids of RB. Our results demonstrate multiple binding partners of RB C-terminal region; a region that is relevant to apoptosis regulation