MARSHALL U COBRE: SAP, A POTENTIAL ZEBRAFISH ONCOGENE

Marshall University, Huntington WV

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Abstract

Strabismus (Stbm), a component of 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 homology to human Chmp1, a Chromatin modifying protein, also known to belong to the family of vesicle trafficking proteins. Similar to stbm, misexpression of sap/chmpl produced convergent extension movement defects in zebrafish and Xenopus. In addition, sap/chmp1 overexpression induces a remarkably early embryonic neoplasm in zebrafish and Xenopus. Sap/Chmp1 physically interacts with Stbm HEK 293T cells and in Xenopus. Sap/Chmp1 colocalizes with Stbm at the plasma membrane compartment where Stbm is localized. Since Sap/Chmp1 shows strong expression in the nucleus, we speculate that nuclear form of Sap/Chmp1 might be responsible for neoplasia formation in zebrafish. We propose to further characterize the neoplasm induced by Sap/Chmp1 overexpression and investigate the mechanism by which it induces tumors in the zebrafish. We hypothesize that Sap/Chmp1 is also overexpressed in certain human tumors. This will be investigated by constructing a human sap/chmp1 cDNA clone and screening an array of cDNAs from a variety of human tumors and their normal tissue counterparts. Cells lines from human tumors shown to overexpress Chmp1 will be used to determine the importance of this gene to neoplastic properties and to begin to investigate the mechanism by which Chmp1 overexpression might contribute to human tumorigenesis.