An ATPase/helicase complex is an essential cofactor for oncogenic transformation by c-Myc

The c-Myc transactivation domain was used to affinity purify tightly associ ated nuclear proteins. Two of these proteins were identified as TIP49 and a novel related protein called TIP48, both of which are highly conserved in evolution and contain ATPase/helicase motifs. TIP49 and TIP48 are complexed with c-Myc in vivo, and binding is dependent on a c-Myc domain essential f or oncogenic activity. A missense mutation in the TIP49 ATPase motif acts a s a dominant inhibitor of c-Myc oncogenic activity but does not inhibit nor mal cell growth, indicating that functional TIP49 protein is an essential m ediator of c-Myc oncogenic transformation. The TIP49 and TIP48 ATPase/helic ase proteins represent a novel class of cofactors recruited by transcriptio nal activation domains that function in diverse pathways.