TGF-beta is a ubiquitously expressed cytokine that signals through the Smad protein family to regulate numerous cellular processes such as embryonic development and tumorigenesis. This signaling is negatively regulated by Ski, the mammalian homolog of the transforming protein of an avian retrovirus that induces oncogenic transformation of chicken embryo cells, and the related protein SnoN. Ski functions by binding to the Smad proteins and preventing their phosphorylation, thereby inhibiting their ability to bind DNA and activate the transcription of downstream genes. Ski will also bind to the Smad proteins specific to bone morphogenic proteins (BMPs) and block BMP signaling in mammalian cells.