This Article Full Text Full Text (PDF) Supplementary Data Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Park, K. Articles by Lee, J.-H. Search for Related Content PubMed PubMed Citation Articles by Park, K. Articles by Lee, J.-H.

Homeobox Msx1 Interacts with p53 Tumor Suppressor and Inhibits Tumor Growth by Inducing Apoptosis

Molecular Therapy Research Center, Sungkyunkwan University, Samsung Medical Center Annex 8F, Kangnam-ku, Seoul, Korea

Requests for reprints: Je-Ho Lee, Molecular Therapy Research Center, Sungkyunkwan University, Samsung Medical Center Annex 8F, 50 ILwon-dong, Kangnam-ku, Seoul, 135-710, Korea. Phone: 82-2-3410-3510; Fax: 82-2-3410-0044; E-mail: jeholee{at}yahoo.com.

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.

Key Words: homeobox Msx1 • p53 protein stabilization • apoptosis • suppression of tumor growth • protein-protein interaction

This article has been cited by other articles:

				L. A. Chalothorn, C. S. Beeman, J. L. Ebersole, G. T. Kluemper, E. P. Hicks, R. J. Kryscio, C. P. DeSimone, and S. C. Modesitt Hypodontia as a risk marker for epithelial ovarian cancer: A case-controlled study J Am Dent Assoc, February 1, 2008; 139(2): 163 - 169. [Abstract] [Full Text] [PDF]

				H. Jung, H.-A. Seong, and H. Ha NM23-H1 Tumor Suppressor and Its Interacting Partner STRAP Activate p53 Function J. Biol. Chem., November 30, 2007; 282(48): 35293 - 35307. [Abstract] [Full Text] [PDF]

				J. Park, K. Kim, E.-J. Lee, Y.-J. Seo, S.-N. Lim, K. Park, S. B. Rho, S.-H. Lee, and J.-H. Lee Elevated level of SUMOylated IRF-1 in tumor cells interferes with IRF-1-mediated apoptosis PNAS, October 23, 2007; 104(43): 17028 - 17033. [Abstract] [Full Text] [PDF]

				E. E. Storm, S. Garel, U. Borello, J. M. Hebert, S. Martinez, S. K. McConnell, G. R. Martin, and J. L. R. Rubenstein Dose-dependent functions of Fgf8 in regulating telencephalic patterning centers Development, May 1, 2006; 133(9): 1831 - 1844. [Abstract] [Full Text] [PDF]