TIP49, but not TRRAP, modulates c-Myc and E2F1 dependent apoptosis.

We previously described two nuclear cofactors, TRRAP and TIP49, that have functional roles in Myc-mediated oncogenesis. We have now expanded the analysis of these Myc-associated cofactors to investigate their roles in apoptosis and cell proliferation. Although TRRAP and TIP49 are both essential for transformation, TIP49 modulates c-Myc-mediated apoptosis whereas disruption of TRRAP activity has no apparent effect on apoptosis. We extended our analysis of TIP49 to show that it also binds to the E2F1 transactivation domain and modulates both transforming and apoptotic activities. These results indicate that individual cofactors differentially potentiate c-Myc and E2F1 functions.