Homeobox Msx1 interacts with p53 tumor suppressor and inhibits tumor growth by inducing apoptosis.
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.
Park
Kyoungsook
K
Molecular Therapy Research Center, Sungkyunkwan University, Samsung Medical Center Annex 8F, 50 Ilwon-dong, Kangnam-ku, Seoul 135-710, Korea.
Kim
Kwangbae
K
Rho
Seung Bae
SB
Choi
Kyusam
K
Kim
Dojin
D
Oh
Sun-Hee
SH
Park
Jinhee
J
Lee
Seung-Hoon
SH
Lee
Je-Ho
JH
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D048708:Cell Growth Processes / Q000502:physiology; D006367:HeLa Cells; D018398:Homeodomain Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D051957:MSX1 Transcription Factor; D051379:Mice; D009368:Neoplasm Transplantation; D019913:Nuclear Localization Signals / Q000378:metabolism; D017434:Protein Structure, Tertiary; D014162:Transfection; D014183:Transplantation, Heterologous; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
D018398:Homeodomain Proteins; D051957:MSX1 Transcription Factor; C484083:MSX1 protein, human; D019913:Nuclear Localization Signals; D016159:Tumor Suppressor Protein p53