MMSC2 - an MMAC1 interacting protein

Abstract

The present invention is directed to the MMSC2 gene, its protein product and the use of the protein to (i) detect mutant MMAC1 proteins, (ii) screen for drugs which can be used for suppressing tumor growth and (iii) identify proteins which interact with the MMAC1 gene or are involved in the tumor suppression pathway of the MMAC1 gene.

What is claimed is:  
     
         1 . A method of screening for drug candidates useful in treating a cancer resulting from a mutation in MMSC2, wherein said method involves mixing a mutant MMSC2 with a wild-type protein, to which wild-type MMSC2 binds, in both the presence of a drug and the absence of said drug and measuring the amount of binding of said mutant MMSC2 with said wild-type protein, wherein if the amount of said binding is greater in the presence of said drug than in the absence of said drug then said drug is a drug candidate for treating said cancer.  
     
     
         2 . The method of  claim 1 , wherein said mutant MMSC2 is a fusion protein and/or said wild-type protein is a fusion protein.  
     
     
         3 . The method of  claim 1 , wherein said wild-type protein is MMAC1.  
     
     
         4 . The method of  claim 1 , wherein said method utilizes a yeast-two hybrid system.  
     
     
         5 . The method of  claim 1 , wherein said test compound is provided in a combinatorial library.  
     
     
         6 . A drug useful for treating a cancer resulting from a mutation in MMSC2 identified by the method of  claim 1 .  
     
     
         7 . A method for screening for drug candidates useful in treating a cancer resulting from a mutation in a protein, which protein when wild-type binds with wild-type MMSC2, wherein said method involves mixing said protein containing said mutation with wild-type MMSC2 in both the presence of a drug and the absence of said drug and measuring the amount of binding of said protein containing said mutation with said wild-type MMSC2, wherein if the amount of said binding is greater in the presence of said drug than in the absence of said drug then said drug is a drug candidate for treating said cancer.  
     
     
         8 . The method of  claim 7 , wherein said wild-type MMSC2 is a fusion protein and/or said mutant protein is a fusion protein.  
     
     
         9 . The method of  claim 7 , wherein said protein is MMAC1.  
     
     
         10 . The method of  claim 7 , wherein said method utilizes a yeast-two hybrid system.  
     
     
         11 . The method of  claim 7 , wherein said test compound is provided in a combinatorial library.  
     
     
         12 . A drug useful for treating a cancer resulting from a mutation in MMSC2 identified by the method of  claim 7 .  
     
     
         13 . A method of screening for drug candidates useful in treating a cancer resulting from a mutation in MMSC2, wherein said method involves mixing a mutant MMSC2 with a wild-type protein, to which wild-type MMSC2 binds, in both the presence of a drug and the absence of said drug and measuring the amount of binding of said mutant MMSC2 with said wild-type protein, wherein if the amount of said binding is less in the presence of said drug than in the absence of said drug then said drug is a drug candidate for treating said cancer.  
     
     
         14 . The method of  claim 13 , wherein said wild-type MMSC2 is a fusion protein and/or said wild-type protein is a fusion protein.  
     
     
         15 . The method of  claim 13 , wherein said wild-type protein is MMAC1.  
     
     
         16 . The method of  claim 13 , wherein said method utilizes a yeast-two hybrid system.  
     
     
         17 . The method of  claim 13 , wherein said test compound is provided in a combinatorial library.  
     
     
         18 . A drug useful for treating a cancer resulting from a mutation in MMSC2 identified by the method of  claim 13 .  
     
     
         19 . A method for screening for drug candidates useful in treating a cancer resulting from a mutation in a protein, which protein when wild-type binds with wild-type MMSC2, wherein said method involves mixing said protein containing said mutation with wild-type MMSC2 in both the presence of a drug and the absence of said drug and measuring the amount of binding of said protein containing said mutation with said wild-type MMSC2, wherein if the amount of said binding is less in the presence of said drug than in the absence of said drug then said drug is a drug candidate for treating said cancer.  
     
     
         20 . The method of  claim 19 , wherein said wild-type MMSC2 is a fusion protein and/or said mutant protein is a fusion protein.  
     
     
         21 . The method of  claim 19 , wherein said protein is MMAC1.  
     
     
         22 . The method of  claim 19 , wherein said method utilizes a yeast-two hybrid system.  
     
     
         23 . The method of  claim 19 , wherein said test compound is provided in a combinatorial library.  
     
     
         24 . A drug useful for treating a cancer resulting from a mutation in MMSC2 identified by the method of  claim 19 .  
     
     
         25 . A method of screening for drug candidates useful in treating a cancer resulting from a mutation in MMSC2, wherein said method involves mixing a wild-type MMSC2 with a wild-type protein, to which wild-type MMSC2 binds, in both the presence of a drug and the absence of said drug and measuring the amount of binding of said mutant MMSC2 with said wild-type protein, wherein if the amount of said binding is less in the presence of said drug than in the absence of said drug then said drug is a drug candidate for treating said cancer.  
     
     
         26 . The method of  claim 25 , wherein said wild-type MMSC2 is a fusion protein and/or said wild-type protein is a fusion protein.  
     
     
         27 . The method of  claim 25 , wherein said wild-type protein is MMAC1.  
     
     
         28 . The method of  claim 25 , wherein said method utilizes a yeast-two hybrid system.  
     
     
         29 . The method of  claim 25 , wherein said test compound is provided in a combinatorial library.  
     
     
         30 . A drug useful for treating a cancer resulting from a mutation in MMSC2 identified by the method of  claim 25 .  
     
     
         31 . A method of screening for drug candidates useful in treating a cancer resulting from a mutation in a protein, which protein when wild-type binds to wild-type MMSC2, wherein said method involves mixing a wild-type MMSC2 with a wild-type protein, to which wild-type MMSC2 binds, in both the presence of a drug and the absence of said drug and measuring the amount of binding of said mutant MMSC2 with said wild-type protein, wherein if the amount of said binding is greater in the presence of said drug than in the absence of said drug then said drug is a drug candidate for treating said cancer.  
     
     
         32 . The method of  claim 31 , wherein said wild-type MMSC2 is a fusion protein and/or said wild-type protein is a fusion protein.  
     
     
         33 . The method of  claim 31 , wherein said wild-type protein is MMAC1.  
     
     
         34 . The method of  claim 31 , wherein said wild-type protein which binds to MMSC2 binds to one or more of the PDZ domains of MMSC2.  
     
     
         35 . The method of  claim 31 , wherein said method utilizes a yeast-two hybrid system.  
     
     
         36 . The method of  claim 31 , wherein said test compound is provided in a combinatorial library.  
     
     
         37 . A drug useful for treating a cancer resulting from a mutation in MMSC2 identified by the method of  claim 31 .  
     
     
         38 . A method of screening for drug candidates useful in treating treating a cancer resulting from a mutation in MMSC2 which comprises the steps of: 
 (a) measuring the activity of a protein selected from the goup consisting of MMSC2 and a protein which binds to MMSC2 in the presence of a drug,    (b) measuring the activity of said protein in the absence of said drug, and    (c) comparing the activity measured in steps (1) and (2),    wherein if there is a difference in activity, then said drug is a drug candidate for treating said cancer resulting from a mutation in MMSC2.    
     
     
         39 . The method of  claim 38 , wherein said protein is MMAC1.  
     
     
         40 . The method of  claim 38 , wherein said test compound is provided in a combinatorial library.  
     
     
         41 . A drug useful for treating a cancer resulting from a mutation in MMSC2 identified by the method of  claim 38 .  
     
     
         42 . A method for identifying a compound that binds to MMSC2 in vitro comprising: 
 contacting a test compound with MMSC2 for a time sufficient to form a complex and    detecting for the formation of a complex by detecting MMSC2 or the compound in the complex,    so that if a complex is detected, a compound that binds to MMSC2 is identified.    
     
     
         43 . The method of  claim 42 , wherein said test compound is provided in a combinatorial library.  
     
     
         44 . A drug useful for treating a cancer resulting from a mutation in MMSC2 identified by the method of  claim 42 .  
     
     
         45 . A method of screening for drug candidates useful in treating a cancer resulting from a mutation in MMSC2, wherein said method comprises treating an animal which is homozygous for MMSC2 containing said mutation with a drug wherein if said animal does not develop cancer said drug is a drug candidate for treating said cancer.  
     
     
         46 . A drug useful for treating a cancer resulting from a mutation in MMSC2 identified by the method of  claim 45 .  
     
     
         47 . A method of screening for drug candidates useful in treating a cancer resulting from a mutation in MMSC2, wherein said method comprises treating an animal which has a tumor and which is homozygous for MMSC2 containing said mutation with a drug, wherein if said tumor regresses said drug is a drug candidate for treating said cancer.  
     
     
         48 . The method of  claim 47  wherein said animal is transgenic for MMSC2 with said mutation.  
     
     
         49 . A drug useful for treating a cancer resulting from a mutation in MMSC2 identified by the method of  claim 47 .  
     
     
         50 . A method of screening for drug candidates useful in treating a cancer resulting from a mutation in MMSC2, wherein said method comprises the steps of: 
 (a) growing a cell culture of cells which are homozygous for MMSC2 containing said mutation in the presence of a drug,    (b) growing a cell culture of cells which contain a wild-type MMSC2 gene, and    (c) growing a cell culture of cells which are homozygous for MMSC2 containing said mutation in the absence of said drug,    wherein if the cells in step (a) behave more like the cells in step (b) than like the cells in step (c) then said drug is a drug candidate for treating said cancer.    
     
     
         51 . A drug useful for treating a cancer resulting from a mutation in MMSC2 identified by the method of claim  50 .