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

Mol Cell. 2000 Feb;5(2):321-30. doi: 10.1016/s1097-2765(00)80427-x.


The c-Myc transactivation domain was used to affinity purify tightly associated 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 for oncogenic activity. A missense mutation in the TIP49 ATPase motif acts as a dominant inhibitor of c-Myc oncogenic activity but does not inhibit normal cell growth, indicating that functional TIP49 protein is an essential mediator of c-Myc oncogenic transformation. The TIP49 and TIP48 ATPase/helicase proteins represent a novel class of cofactors recruited by transcriptional activation domains that function in diverse pathways.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • ATPases Associated with Diverse Cellular Activities
  • Adenosine Triphosphatases / metabolism*
  • Amino Acid Sequence
  • Animals
  • Binding Sites
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism
  • Cell Transformation, Neoplastic*
  • DNA Helicases / metabolism*
  • Gene Expression Regulation
  • Molecular Sequence Data
  • Mutation
  • Protein Binding
  • Proto-Oncogene Proteins c-myc / metabolism*
  • Rats
  • Saccharomyces cerevisiae / enzymology
  • Sequence Homology, Amino Acid


  • Carrier Proteins
  • Proto-Oncogene Proteins c-myc
  • Adenosine Triphosphatases
  • ATPases Associated with Diverse Cellular Activities
  • DNA Helicases
  • RUVBL2 protein, human
  • Ruvbl1 protein, rat