CHARACTERIZATION OF HUMAN HOMOLOGS OF THE DROSOPHILA-7 IN-ABSENTIA (SINA) GENE

Studies of Drosophila photoreceptor development have illustrated the m eans by which signal transduction events regulate cell fate decisions in a multicellular organization. Development of the R7 photoreceptor i s best understood, and its formation is dependent on the seven in abse ntia (sina) gene. We have characterized two highly conserved human hom ologs of sina, termed SIAH1 and SIAH2. SIAH1 maps to chromosome 16q12 and encodes a 282-amino-acid protein with 76% amino acid identity to t he Drosophila SINA protein. SIAH2 maps to chromosome 3q25 and encodes a 324-amino-acid protein that shares 68% identity with Drosophila SINA and 77% identity with human SLAH1. SIAH1 and SIAH2 were expressed in many normal and neoplastic tissues, and only subtle differences in the ir expression were noted. However, one of three murine homologs, Siah1 B was strongly induced in fibroblasts undergoing apoptotic cell death. While a previous study suggested that SINA was a nuclear protein, epi tope-tagged SINA and SIAH1 proteins were found in the cytoplasm of Dro sophila and mammalian cells. Their substantial evolutionary conservati on, role in specifying cell fate, and activation in apoptotic cells su ggest the SIAH proteins have important roles in vertebrate development . Furthermore, given the role of sina in Drosophila photoreceptor deve lopment, SIAH2 is a candidate for the Usher syndrome type 3 gene at ch romosome 3q21-q25. (C) 1997 Academic Press.