Replication protein

Abstract

This invention relates to a screening method for the identification of agents which modulate the activity of a DNA replication protein as a target for intervention in cancer therapy and includes agents which modulate said activity. The invention also relates to the use of the DNA replication protein, and its RNA transcripts in the prognosis and diagnosis of proliferative disease e.g., cancer.

1 - 33 . (canceled) 
     
     
         34 . A diagnostic method for the identification of a cancer comprising detecting the presence of a Ciz1 polypeptide, wherein the presence or expression of said Ciz1 polypeptide is indicative of the presence of cancer. 
     
     
         35 . The diagnostic method according to  claim 34 , wherein said method comprises one or more of the following steps:
 (i) contacting a sample isolated from a subject to be tested with an agent which specifically binds a Ciz1 polypeptide; and   (ii) detecting or measuring the binding of said agent to said Ciz1 polypeptide.   
     
     
         36 . The method of  claim 34 , wherein said Ciz1 polypeptide comprises an amino-acid sequence selected from the group consisting of SEQ ID NO: 29-44, 47, 48, 58-64 and 65. 
     
     
         37 . The method of  claim 36 , wherein said Ciz1 polypeptide comprises an amino-acid sequence selected from the group consisting of SEQ ID NO: 58-64 and 65. 
     
     
         38 . The method of  claim 37 , wherein said Ciz1 polypeptide comprises an amino-acid sequence of SEQ ID NO: 64. 
     
     
         39 . The method of  claim 35 , wherein said agent is an antibody. 
     
     
         40 . The method of  claim 39 , wherein said antibody is a monoclonal antibody. 
     
     
         41 . The method of  claim 35 , wherein said agent is an aptamer. 
     
     
         42 . The method of  claim 39 , wherein said Ciz1 polypeptide comprises an amino-acid sequence of SEQ ID: 64. 
     
     
         43 . The method according to  claim 34 , wherein the cancer is a pediatric cancer selected from the group consisting of retinoblastoma, neuroblastoma, Burkett lymphoma, medulloblastoma, and Ewings Sarcoma family tumors. 
     
     
         44 . The method according to  claim 34 , wherein the cancer is carcinoma, adenocarcinoma, lymphoma or leukemia. 
     
     
         45 . The method according to  claim 34  wherein the cancer is liver, lung or skin cancer. 
     
     
         46 . The method of  claim 35 , wherein said agent specifically binds to a Ciz1 polypeptide at a junction sequence translated from an alternatively spliced Ciz1 transcript. 
     
     
         47 . The method of  claim 46 , wherein said agent specifically binds a junction sequence of a Ciz1 polypeptide created when the amino-acid sequence VEEELCKQ is missing. 
     
     
         48 . The method of  claim 35 , wherein said agent specifically binds to a Ciz1 polypeptide at a junction sequence created from an alternatively spliced Ciz1 transcript that is missing the nucleotide sequence of SEQ ID NO: 56. 
     
     
         49 . The method of  claim 46 , wherein said agent is an antibody. 
     
     
         50 . The method of  claim 47 , wherein said agent is an antibody. 
     
     
         51 . The method of  claim 48 , wherein said agent is an antibody. 
     
     
         52 . The method of  claim 49 , wherein said cancer is lung cancer. 
     
     
         53 . The method of  claim 50 , wherein said cancer is lung cancer. 
     
     
         54 . The method of  claim 51 , wherein said cancer is lung cancer.