The oncoprotein Qin is a member of the winged helix family of transcriptional regulators. The region C-terminal to its winged helix DNA-binding domain is required for transformation of chicken embryo fibroblasts. We isolated the corepressor TLE1 as a binding partner for Qin in a yeast two-hybrid screen and localized the TLE1-binding region to a 60 amino-acid stretch directly C-terminal of the winged helix domain of Qin. We show in vivo interaction of full-length Qin and TLE1 in a mammalian two-hybrid system. Coexpression of TLE1-binding Qin and TLE1 induces phosphorylation of TLE1. The DNA-binding activity of Qin is not required for this function. Binding of Qin to TLE1 correlates with Qin-induced transformation. Addition of the TLE1-binding motif WRPW to the C-terminus of a transformation-defective Qin deletion mutant restores binding to TLE1 and significantly enhances transformation. Expression of TLE1 in CEF by the retroviral vector RCAS enhances cell growth and induces formation of agar colonies.