POST-TRANSLATIONAL MODIFICATION OF SURVIVIN: A NOVEL THERAPEUTIC APPROACH FOR CA

Rhode Island Hospital, Providence RI

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Abstract

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Survivin is a cancer-associated protein with dual functions as a cell death inhibitor and as a cell division regulator. It is highly expressed in chemo-resistant tumors, making it a prognostic marker for high-risk disease. Tumor cells that express Survivin cannot compensate for a dysfunctional Survivin protein and undergo rapid and spontaneous cell death in its absence. The biochemical mechanism by which Survivin binds to itself and to its partner proteins is unclear. Our preliminary data suggests that Survivin is modified by acetylation, implicating this biochemical process as a mechanism of its function and stability. The short-term goals of this proposal are to identify the proteins that acetylate Survivin, identify the specific residues at which the acetylation occurs and determine how these biochemical modifications alter the prosurvival function of Survivin in human tumor cells. The long-term goals of this project are to provide insight into unexplored biochemical mechanisms that will ultimately lead to novel therapies directed to pivotal steps in tumor cell death pathways.