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p73 shares high sequence homology with the tumor suppressor p53. Like p53, ectopic overexpression of p73 induces cell cycle arrest and/or apoptosis, and these biological activities are linked to its sequence-specific transactivation function. The COOH-terminal region of p73 is unique and has a function to modulate DNA-binding ability and transactivation activity. To identify and characterize cellular proteins that interact with the COOH-terminal region of p73α and regulate its activity, we employed a yeast-based two-hybrid screen with a human fetal brain cDNA library. We found MM1, a nuclear c-Myc-binding protein, was associated with p73α in both yeast two-hybrid and in vitropull-down assays. In mammalian cells, MM1 co-immunoprecipitated with p73α, whereas p73β and tumor suppressor p53 did not interact with MM1. Overexpression of MM1 in p53-deficient osteosarcoma SAOS-2 cells enhanced the p73α-dependent transcription from the p53/p73-responsiveBaxand PG13promoters, whereas p73β- and p53-mediated transcriptional activation was unaffected in the presence of MM1. MM1 also stimulated the p73α-mediated growth suppression in SAOS-2 cells. More importantly, we found that c-Myc was physically associated with p73α and significantly impaired the transcriptional activity of p73α on Baxand p21waf1promoters. Expression of MM1 strongly reduced the c-Myc-mediated inhibitory activity on p73α. These results suggest that MM1 may act as a molecular partner for p73 to prevent the c-Myc-mediated inhibitory effect on its activity.