This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor the Center, which is not necessarily the institution for the investigator.Strabismus (Stbm), a component of the non-canonical Wnt signaling pathway, modulates convergent extension movements in zebrafish and Xenopus. Sap (Stbm associated protein) was identified from yeast two-hybrid screen (using Stbm as a bait). Sap has homolog y to human Chmp-1, a Chromatin modifying protein, also known to belong to the family of vesicle trafficking proteins. Similar to stbm, misexpression of sap/chmp-1 produced convergent extension movement defects in zebrafish and Xenopus. In addition, sap/ch mpI over expression induces a remarkably early embryonic neoplasm in zebrafish and Xenopus. Sap Chmp-1 physically interacts with Stbrn in HEK 293T cells and in Xenopus. Sap/Chmp-1 colocalizes with Stbm at the plasma membrane compartment where Stbm is lo calized.Since Sap/Chmp-1 shows strong expression in the nucleus, we speculate that the nuclear form of Sap/Chmpl might be responsible for neoplasia formation in zebrafish. We propose to further characterize the neoplasm induced by Sap/Chmp-1 overexpressi on and investigate the mechanism by which it induces tumors in the zebrafish. We hypothesize that Sap/Chmp-1 is also overexpressed in certain human tumors. This will be investigated by constructing a human sap/chmp-1 cDNA clone and screening an array of c DNAs from a variety of human tumors and their normal tissue counterparts. Cells lines from human tumors shown to overexpress Chmp 1 will be used to determine the importance of this gene to neoplastic properties and to begin to investigate the mechani sm by which Chmp-1 overexpression might contribute to human tumorigenesis.
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