Tumour Suppressor Protein

Abstract

We describe a polypeptide which binds and modulates the activity of a tumour suppressor polypeptide, for example p53; a nucleic acid molecule encoding said protein and screening methods which modulate the binding activity of said polypeptide for its target polypeptide(s).

1 - 4 . (canceled) 
     
     
         5 . The isolated nucleic acid molecule according to  claim 6  wherein said polypeptide consists of the amino acid sequence set forth in SEQ ID NO: 1. 
     
     
         6 . An isolated nucleic acid molecule comprising a nucleotide sequence that encodes a polypeptide comprising the amino acid sequence set forth in SEQ ID NO: 1. 
     
     
         7 . The isolated nucleic acid molecule according to  claim 6 , wherein said nucleic acid molecule comprises the nucleic acid sequence set forth in SEQ ID NO: 2 or a nucleic acid molecule which hybridises to the sequence set forth in SEQ ID NO: 2 under stringent hybridisation conditions, wherein said nucleic acid sequence encodes the polypeptide comprising the amino acid sequence set forth in SEQ ID NO: 1. 
     
     
         8 . The isolated nucleic acid molecule according to  claim 6  wherein said nucleic acid molecule consists of the nucleic acid sequence set forth in SEQ ID NO: 2. 
     
     
         9 . The isolated nucleic acid molecule according to  claim 6  wherein said molecule is a cDNA. 
     
     
         10 . The isolated nucleic acid molecule according to  claim 6  wherein said molecule is genomic DNA. 
     
     
         11 . A vector comprising the nucleic acid molecule according to  claim 6 . 
     
     
         12 . A method for producing a polypeptide, comprising transforming or transfecting a cell with the vector according to  claims 11 ; growing said cell in conditions conducive to the manufacture of said polypeptide; and purifying said polypeptide from said cell, or its growth environment. 
     
     
         13 - 18 . (canceled) 
     
     
         19 . A composition comprising the nucleic acid molecule according to  claim 6  and a pharmaceutically-acceptable carrier. 
     
     
         20 . The composition according to  claim 6 , wherein said nucleic acid molecule is an inhibitory RNA molecule. 
     
     
         21 . The composition according to  claim 6 , wherein said nucleic acid molecule is an antisense nucleic acid molecule. 
     
     
         22 . The composition according to  claim 20 , wherein said inhibitory RNA molecule is designed to that part of said nucleic acid sequence which encodes amino acid residue 1 to 483 set forth in SEQ ID NO: 1. 
     
     
         23 . The composition according to  claim 22 , said nucleic acid molecule is provided as a transcription cassette comprising a nucleic acid sequence operatively linked to a promoter which promoter transcribes said nucleic acid molecule to produce an antisense nucleic acid molecule, said sequence selected from the group consisting of:
 i) a nucleic acid sequence, or part thereof, set forth in SEQ ID NO: 2;   ii) a nucleic acid sequence which hybridises to the sense sequence set forth in SEQ ID NO: 2  FIG. 1   b —and which encodes the polypeptide set forth in SEQ ID NO: 1.   
     
     
         24 . (canceled) 
     
     
         25 . The composition according to  claim 22  wherein said cassette is provided with at least two promoters adapted to transcribe both sense and antisense strands of said nucleic acid molecule. 
     
     
         26 . The composition according to  claim 22  wherein said cassette comprises a nucleic acid molecule wherein said molecule comprises a first part linked to a second part wherein said first and second parts are complementary over at least part of their sequence and further wherein transcription of said nucleic acid molecule produces an RNA molecule which forms a double stranded region by complementary base pairing of said first and second parts. 
     
     
         27 . The composition according to  claim 26  wherein said first and second parts are linked by at least one nucleotide base. 
     
     
         28 . The composition according to  claim 23  wherein said cassette is part of a vector. 
     
     
         29 - 34 . (canceled) 
     
     
         35 . The composition according to  claim 21 , wherein said antisense is designed to that part of said nucleic acid sequence which encodes amino acid residue 1 to 483 set forth in SEQ ID NO: 1. 
     
     
         36 . The isolated nucleic acid molecule according to  claim 6 , comprising a nucleotide sequence that encodes amino acids 1-483 of SEQ ID NO: 1. 
     
     
         37 . The isolated nucleic acid molecule according to  claim 6 , wherein at least one residue of the encoded polypeptide is ubuiqunated. 
     
     
         38 . The isolated nucleic acid molecule according to  claim 6 , wherein the encoded polypeptide is acetylated. 
     
     
         39 . The isolated nucleic acid molecule according to  claim 38 , wherein the amino-terminus of the encoded polypeptide is acetylated. 
     
     
         40 . The isolated nucleic acid molecule according to  claim 6 , wherein the encoded polypeptide is amidated. 
     
     
         41 . The isolated nucleic acid molecule according to  claim 40 , wherein the carboxyl-terminus of the encoded polypeptide is amidated.