Bcl-g polypeptides, encoding nucleic acids and methods of use

Abstract

The invention provides Bcl-G polypeptides and encoding nucleic acids. Bcl-G polypeptides include Bcl-G L and Bcl-G S . The invention also provides mouse Bcl-G. The invention also provides vectors containing Bcl-G nucleic acids, host cells containing such vectors, Bcl-G anti-sense nucleic acids and related compositions. The invention additionally provides Bcl-G oligonucleotides that can be used to hybridize to or amplify a Bcl-G nucleic acid. Anti-Bcl-G specific antibodies are also provided. Further provided are kits containing Bcl-G nucleic acids or Bcl-G specific antibodies. Such kits and reagents can be used to diagnose cancer, monitor response to therapy, or predict the prognosis of a cancer patient. The invention additionally provides methods of modulating apoptosis using Bcl-G polypeptides, encoding nucleic acids, or compounds that modulate the activity or expression of Bcl-G polypeptides. The methods for modulating apoptosis can be used to treat diseases such as cancer.

What is claimed is: 
     
         1 . A method of identifying an effective agent that alters the association of a Bcl-G with a Bcl-G associated polypeptide (BAP), comprising the steps of:
 (a) contacting said Bcl-G and said BAP polypeptide, under conditions that allow said Bcl-G and BAP polypeptide to associate, with a compound; and   (b) detecting the altered association of said Bcl-G and BAP polypeptide, thereby identifying a compound that is an effective agent for altering the association of said Bcl-G with BAP.   
     
     
         2 . The method of  claim 1 , wherein said compound is a compound. 
     
     
         3 . The method of  claim 1 , wherein said compound is a drug. 
     
     
         4 . The method of  claim 1 , wherein said compound is a polypeptide. 
     
     
         5 . A method for modulating an activity mediated by a Bcl-G polypeptide, comprising contacting said Bcl-G polypeptide with an effective, modulating amount of an agent identified by  claim 1 . 
     
     
         6 . The method of  claim 5 , wherein said modulated activity is the binding of Bcl-G to a Bcl-2 family member. 
     
     
         7 . A therapeutic composition comprising a pharmaceutically acceptable carrier and a compound selected from the group consisting of a Bcl-G polypeptide, a functional fragment of said Bcl-G, a Bcl-G modulating compound identified according to  claim 1 , and an anti-Bcl-G antibody. 
     
     
         8 . A method of treating a pathology characterized by abnormal cell proliferation, comprising administering an effective amount of the composition according to  claim 7 . 
     
     
         9 . A method of modulating the level of apoptosis in a cell, comprising contacting the cell with a compound that effectively alters the association of Bcl-G with a Bcl-G-associated-protein in the cell, or that effectively alters the activity of a Bcl-G in the cell. 
     
     
         10 . A chimeric protein comprising a domain selected from the group consisting of BH3 (SEQ ID NOS:5 or 9) and BH2 (SEQ ID NOS:6 or 18). 
     
     
         11 . A method of modulating interactions between Bcl-G and Bcl-2, comprising contacting a Bcl-G polypeptide with the agent of  claim 1 .