Yaf2 inhibits Myc biological function

The proto-oncogenes of the myelocytomatosis viral oncogene homolog (MYC) family, including MYC, MYCN and MYCL, encode nuclear proteins that act as transcription factors. The Myc protein is the best studied member of this family and is involved in cell cycle regulation, differentiation and cell death. We have previously demonstrated that the zinc-finger protein Yaf2 interacts with the central region of MycN and enhances MycN dependent transcriptional activation. Here we show that Yaf2 also binds to the Myc protein in vivo and in vitro. In contrast to the activating effect on MycN function, Yaf2 inhibits Myc mediated transactivation and transformation. This differential influence on two members of the Myc family gives insight into a new mechanism to modulate the biological activities of Myc transcription factors.