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

Kyoungsook Park, Kwangbae Kim, Seung Bae Rho, Kyusam Choi, Dojin Kim, Sun-Hee Oh, Jinhee Park, Seung-Hoon Lee, Je-Ho Lee
2005 Cancer Research  
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.
more » ... rafts 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 fatcat:lkckpgirhne2bl4l77vl3ikjwa