Mammalian tumor susceptibility gene products and their uses

Abstract

The present invention provides methods and compositions for regulating ubiquitination in a cell. In particular, the present invention provides purified polypeptides comprising an ubiquitination-regulating domain. The invention also provides methods of using such polypeptides for screening for agents, for producing antibodies, and for treatment of diseases, e.g., proliferative diseases, neurodegenerative diseases, autoimmune diseases, metabolic disease and developmental abnormalities. The invention further provides antibodies that bind an ubiquitination-regulating domain and agents and antibodies that regulate ubiquitination in cells, e.g., by modulating the interaction between a TSG101 protein and an MDM2 protein.

1 - 42 . (canceled) 
     
     
         43 . An isolated monoclonal antibody that binds specifically to a polypeptide comprising the amino acid sequence of SEQ ID NO: 1, wherein said antibody binds specifically to a ubiquitination-regulating domain of said polypeptide; and
 wherein said antibody binds specifically to an epitope found in amino acid residues 1-250 of SEQ NO: 1 and by so binding.   
     
     
         44 . An isolated monoclonal antibody that binds specifically to a polypeptide comprising a ubiquitination-regulating domain of a human TSG101 protein comprising the amino acid sequence of SEQ ID NO: 1, wherein said antibody binds specifically to an epitope in the ubiquitination-regulating domain of TSG101 protein found in amino acid residues 50-140 of SEQ ID NO:1. 
     
     
         45 . An isolated monoclonal antibody that binds specifically to a polypeptide comprising a ubiquitination-regulating domain of a human TSG101 protein comprising the amino acid sequence of SEQ ID NO: 1, wherein said antibody binds specifically to an epitope in the ubiquitination-regulating domain of TSG101 protein found in amino acid residues 140-250 of SEQ ID NO: 1. 
     
     
         46 . A pharmaceutical composition for treatment of diseases involving TSG 101 comprising:
 an isolated monoclonal antibody that binds specifically to a polypeptide comprising an ubiquitination-regulating domain, of a human TSG101 protein wherein said antibody binds specifically to an epitope in the ubiquitination regulating domain of TSG101 protein found in amino acid residues 1-250 of SEQ ID NO: 1, and a pharmaceutically acceptable excipient.   
     
     
         47 . A method for treatment of diseases involving TSG101-mediated abnormalities, said method comprising:
 administering to a subject suffering from a disease involving a TSG101-mediated abnormality an effective amount of the pharmaceutical composition of  claim 46 .