TUMOR SUPPRESSORS & CELL CYCLE CONTROL

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Cell cycle and growth are critical for normal human health. Tumor suppressors control these functions and mutations or alterations of these suppressor molecules can be associated with the uncontrolled growth of tumors. We are studying the retinoblastoma protein and a new protein RIZ that binds to Rb and may itself be a tumor suppressor. Rb binds to cellular proteins through a region known as the pocket domain that consists of two regions (A and B) connected by a flexible segment. Most mutations in human tumors map to the "pocket" domain. Small crystals have already been produced of the pocket domain in our laboaratory. Previously, the structure of the A region of the pocket domain was determined, but the function of this segment alone is not known. Our goal is to solve the structure of the full "pocket" domain and to extend the studies to binding interactions with RIZ.