Heterodimers of the SnoN and Ski oncoproteins form preferentially over homodimers and are more potent transforming agents

sno is a member of the ski oncogene family and shaves ski's ability to tran sform avian fibroblasts and induce muscle differentiation. Ski and SnoN are transcription factors that form both homodimers and heterodimers. They rec ognize a specific DNA binding site (GTCTAGAC) through which they repress tr anscription. Efficient homodimerization of Ski, mediated by a bipartite C-t erminal domain consisting of five tandem repeats (TR) and a leucine zipper (LZ), correlates with efficient DNA binding and cellular transformation. Th e present study assesses the role of SnoN homodimerization and SnoN:Ski het erodimerization in the activities of these proteins. Unlike Ski, efficient homodimerization by SnoN is shown to require an upstream region of the prot ein in addition to the TR/LZ domain. Deletion of the TR/LZ from SnoN decrea ses its activity in transcriptional repression and cellular transformation. When coexpressed in vitro, c-Ski and SnoN preferentially form heterodimers . In vivo, they form heterodimers that bind the GTCTAGAC element. Tethered Ski:Sno heterodimers that lack TR/LZ domains are more active than either th eir monomeric counterparts, tethered Ski:Ski homodimers or full-length SnoN and c-Ski, This work demonstrates, for the first time, the differences bet ween dimer formation by Ski and SnoN and underscores the importance of dime rization in their activity.