Novel agent for inducing apoptosis comprising Msx1 or a gene encoding the same as an active ingredient

Abstract

The present invention relates to a novel use of Msx1 protein or a nucleotide encoding the same for inducing apoptosis. The Msx1 of the present invention induces apoptosis through direct interaction with p53 via a homeodomain and such interaction leads to increased stability, and/or nuclear localization of p53 in cells. The Msx1 or homeodomain thereof can be effectively used for the treatment of tumors, in which wild-type p53 protein has lost its function by some mechanism that inactivates p53 proteins.

1 . A method of inducing apoptosis comprising a step of administering to a tissue or a subject associated with a disease condition a therapeutically effective amount of Msx1 protein or a nucleotide sequence encoding the same.  
     
     
         2 . The method of  claim 1 , wherein said Msx1 or a nucleotide sequence encoding the same is a homeodomain of Msx1 or a nucleotide sequence encoding the same.  
     
     
         3 . The method of  claim 2 , wherein said induction of apoptosis involves direct interaction of Msx1 or homeodomain thereof with p53 protein.  
     
     
         4 . The method of  claim 3 , wherein said interaction of Msx1 or a homeodomain thereof with p53 protein leads to increased stability, and/or nuclear localization of p53.  
     
     
         5 . The method of  claim 4 , wherein said disease condition is a tumor.  
     
     
         6 . The method of  claim 5 , wherein said tumor comprises colon cancer, cervical cancer, ovarian cancer, lung cancer, lymphoma, breast cancer, prostate cancer, and renal cell cancer.  
     
     
         7 . The method of  claim 6 , wherein said tumor contains p53 protein.  
     
     
         8 . The method of  claim 7 , wherein said p53 protein is of endogenous or exogenous origin.  
     
     
         9 . The method of  claim 7 , wherein said p53 is an inactivated protein.  
     
     
         10 . A method of modulating p53 protein activity in a tissue or a subject comprising a step of administering to a tissue or a subject associated with a disease condition a therapeutically effective amount of Msx1 protein or a nucleotide sequence encoding the same.  
     
     
         11 . The method of  claim 10 , wherein said Msx1 or a nucleotide sequence encoding the same is a homeodomain of Msx1 or a nucleotide sequence encoding the same.  
     
     
         12 . The method of  claim 11 , wherein p53 protein is of endogenous or exogenous origin.  
     
     
         13 . The method of  claim 12 , wherein said modulation of p53 involves direct interaction of Msx1 or a homeodomain thereof.  
     
     
         14 . The method of  claim 13 , wherein said interaction of Msx1 or homeodomain thereof with p53 protein leads to increased stability, and/or nuclear localization of p53.  
     
     
         15 . The method of  claim 14 , wherein said condition is a tumor.  
     
     
         16 . The method of  claim 15 , wherein said tumor comprises colon cancer, cervical cancer, ovarian cancer, lung cancer, lymphoma, breast cancer, prostate cancer, and renal cell cancer.  
     
     
         17 . A pharmaceutical composition for inducing apoptosis in a target mammalian tissue comprising Msx1 protein or a nucleotide sequence encoding the same as an active ingredient, and a pharmaceutically acceptable carrier or excipient.  
     
     
         18 . The pharmaceutical composition of  claim 17 , wherein said target mammalian tissue is associated with a disease condition selected from the group of solid tumors comprising colon cancer, cervical cancer, ovarian cancer, lung cancer, lymphoma, breast cancer, and prostate cancer.  
     
     
         19 . A pharmaceutical composition for modulating p53 in a target mammalian tissue comprising Msx1 protein or a nucleotide sequence encoding the same as an active ingredient, and a pharmaceutically acceptable carrier or excipient.  
     
     
         20 . The pharmaceutical composition of  claim 19 , wherein said target mammalian tissue is associated with a disease condition selected from the group of solid tumors comprising colon cancer, cervical cancer, ovarian cancer, lung cancer, lymphoma, breast cancer, prostate cancer, and renal cell cancer.