A carboxyl-terminal region of the ski oncoprotein mediates homodimerization as well as heterodimerization with the related protein SnoN.

Ski is a nuclear oncoprotein, and possibly a transcriptional factor, that has been shown to be involved in both transformation and myogenesis. In attempts to understand the molecular mechanisms underlying the function of Ski, the protein-protein interactions of Ski with itself and with its close relative, SnoN, were investigated. It was found that while both v-Ski and c-Ski bound themselves and each other as bacterial fusion proteins, only c-Ski formed homodimers that could be detected by covalent cross-linking of the native in vitro translated protein in solution. The results also showed that c-Ski formed heterodimers with SnoN. Deletion analysis showed that the carboxyl-terminal third of c-Ski, which is deleted in v-Ski, was required for stable dimer formation in solution. This region consists of two predicted structural motifs that constitute the c-Ski dimerization domain. The more amino-terminal motif is predicted to be mostly alpha helical and is comprised of five tandem repeats of 25 amino acids each and was required for c-Ski dimerization. The second motif is a predicted leucine zipper that was not required for dimerization but greatly increased the fraction of Ski protein detected as dimers. This minor c-Ski homodimerization domain appeared to be required for Ski-Sno heterodimer formation.