Characterization of human homologs of the Drosophila seven in absentia (sina) gene.

Studies of Drosophila photoreceptor development have illustrated the means by which signal transduction events regulate cell fate decisions in a multicellular organization. Development of the R7 photoreceptor is best understood, and its formation is dependent on the seven in absentia (sina) gene. We have characterized two highly conserved human homologs of sina, termed SIAH1 and SIAH2. SIAH1 maps to chromosome 16q12 and encodes a 282-amino-acid protein with 76% amino acid identity to the 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 SIAH1. SIAH1 and SIAH2 were expressed in many normal and neoplastic tissues, and only subtle differences in their expression were noted. However, one of three murine homologs, Siah1B, was strongly induced in fibroblasts undergoing apoptotic cell death. While a previous study suggested that SINA was a nuclear protein, epitope-tagged SINA and SIAH1 proteins were found in the cytoplasm of Drosophila and mammalian cells. Their substantial evolutionary conservation, role in specifying cell fate, and activation in apoptotic cells suggest the SIAH proteins have important roles in vertebrate development. Furthermore, given the role of sina in Drosophila photoreceptor development, SIAH2 is a candidate for the Usher syndrome type 3 gene at chromosome 3q21-q25.