Abstract
sno is a member of the ski oncogene family and shares ski 's ability to transform avian fibroblasts and induce muscle differentiation. Ski and SnoN are transcription factors that form both homodimers and heterodimers. They recognize a specific DNA binding site (GTCTAGAC) through which they repress transcription. Efficient homodimerization of Ski, mediated by a bipartite C-terminal domain consisting of five tandem repeats (TR) and a leucine zipper (LZ), correlates with efficient DNA binding and cellular transformation. The present study assesses the role of SnoN homodimerization and SnoN:Ski heterodimerization in the activities of these proteins. Unlike Ski, efficient homodimerization by SnoN is shown to require an upstream region of the protein in addition to the TR/LZ domain. Deletion of the TR/LZ from SnoN decreases its activity in transcriptional repression and cellular transformation. When co-expressed in vitro, c-Ski and SnoN preferentially form heterodimers. In vivo, they form heterodimers that bind the GTCTAGAC element. Tethered Ski:Sno hetero-dimers that lack TR/LZ domains are more active than either their monomeric counterparts, tethered Ski:Ski homodimers or full-length SnoN and c-Ski. This work demonstrates, for the first time, the differences between dimer formation by Ski and SnoN and underscores the importance of dimerization in their activity.