Homeobox Msx1 interacts with p53 tumor suppressor and inhibits tumor growth by inducing apoptosis

Cancer Res. 2005 Feb 1;65(3):749-57.


The stability of wild-type p53 is critical for its apoptotic function. In some cancers, wild-type p53 is inactivated by interaction with viral and cellular proteins, and restoration of its activity has therapeutic potential. Here, we identify homeobox Msx1 as a p53-interacting protein and show its novel function as a p53 regulator. Overexpression of homeobox Msx1 induced apoptosis of cancer cells harboring nonfunctional wild-type p53 and suppressed growth of human tumor xenografts in nude mice. The homeodomain of Msx1 functions as a protein-protein interacting motif rather than a DNA-binding domain and is essential for stabilization, nuclear accumulation, and apoptotic function of wild-type p53. The identification of a novel function of Msx1 as a p53 regulator may open new avenues for developing improved molecular therapies for tumors with a nonmutational p53 inactivation mechanism.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / physiology*
  • Cell Growth Processes / physiology
  • HeLa Cells
  • Homeodomain Proteins / biosynthesis
  • Homeodomain Proteins / genetics
  • Homeodomain Proteins / metabolism*
  • Humans
  • MSX1 Transcription Factor
  • Mice
  • Neoplasm Transplantation
  • Nuclear Localization Signals / metabolism
  • Protein Structure, Tertiary
  • Transfection
  • Transplantation, Heterologous
  • Tumor Suppressor Protein p53 / metabolism*


  • Homeodomain Proteins
  • MSX1 Transcription Factor
  • MSX1 protein, human
  • Nuclear Localization Signals
  • Tumor Suppressor Protein p53