SKI is a nuclear protein that forms homodimers and heterodimers and binds to DNA to function as transcriptional activators and repressors. The SKI oncoprotein dramatically affects cell growth, differentiation, and/or survival. SKI was shown to act in distinct signaling pathways including those involving nuclear receptors, transforming growth factor beta, and tumor suppressors. SKI inhibits transforming growth factor-beta (TGF-beta) signaling through interaction with Smad proteins. SKI represses Smad-mediated transcriptional activation, probably through its action as a transcriptional co-repressor. SKI also inhibits TGF-beta-induced downregulation of genes such as c-myc.