| Independent studies have shown that Sina and its highly related mammalian homologues Siah 1 and Siah 2 bind to the DCC ( deleted in colorectal cancer ) protein and promote its proteolysis via the ubiquitin proteasome pathway . ^^^ To determine the roles of mammalian Siahs in proteolysis and their interactions with target proteins , we sought to define Siah 1 domains critical for regulation of DCC . ^^^ Mutant Siah 1 proteins , harboring missense mutations in the carboxy ( C ) terminal domain analogous to those present in Drosophila sina loss of function alleles , failed to promote DCC degradation . ^^^ Point mutations and deletion of the amino ( N ) terminal RING finger domain of Siah 1 abrogated its ability to promote DCC proteolysis . ^^^ In the course of defining Siah 1 sequences required for DCC degradation , we found that Siah 1 is itself rapidly degraded via the proteasome pathway , and RING domain mutations stabilized the Siah 1 protein . ^^^ |