Induction of apoptosis by the prodomain of IL1 alpha

Northern California Institute Res &Educ, San Francisco CA

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Abstract

This application describes the properties of the N-terminal propiece of the Interleukin-1alpha precursor molecule for the specific induction of tumor cell apoptosis. No function has ever been attributed to this propiece fragment. We describe the mechanisms of cellular entry, nuclear targeting, interaction with pre-mRNA splicing factors, and modulation of alternative splicing of an apoptotic protein by the IL-1a propiece. The result is tumor cell apoptosis by a non-p53-mediated mechanism. A detailed examination of the interaction of this protein with members of the family of RNA splicing proteins, as outlined in this proposal, may be expected to provide key insights into the induction of apoptosis in tumor cells and permit the development of novel therapeutic agents based on this pathway.