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

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

Park K, Kim K, Rho SB, Choi K, Kim D, Oh SH, Park J, Lee SH, Lee JH.

Molecular Therapy Research Center, Sungkyunkwan University, Samsung Medical
Center Annex 8F, 50 Ilwon-dong, Kangnam-ku, Seoul 135-710, Korea.

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.

PMID: 15705871 [PubMed - indexed for MEDLINE]


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