MECHANISM OF NON-CLASSICAL RELEASE OF THE ANGIOGENESIS REGULATOR, IL1-ALPHA

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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. The project by I. Prudovsky represents a new direction for his long-term productive interest in non-classical release mechanisms for proteins lacking signal-peptides. These studies have evolved through collaboration with T. Maciag, although the hypothesis and approach were developed independently by Dr. Prudovsky. This project proposes to examine the mechanism of release of the pro-inflammatory cytokine IL1-alpha, and how this mechanism differs from that of the pro-angiogenic factor FGF1. These studies will have translational potential and therapeutic implications for the design of novel inhibitors of IL1-alpha and FGF1 release. It is anticipated that this project will be interactive with Project 2 (L. Liaw) in examining the release of IL1-alpha from GIST tumors or surrounding inflammatory cells. Furthermore it is anticipated that this project will be interactive with both of our senior recruits (Projects 7 and 8), whose area of research interest will involve inflammatory mechanisms in the vessel wall.