Methods for identifying modulators of apoptosis

Abstract

The invention provides a method of identifying an effective compound that modulates the binding of Humanin to Bax or Bid. The invention also provides a method of identifying an effective compound that modulates an activity of Bax or Bid. In addition, the invention provides a method of identifying a Humanin-like compound that binds to Bax or Bid or modulates an activity of Bax or Bid, or inhibits the apoptotic activity of Bax or Bid. The invention further provides an isolated polypeptide containing a mitochondrial-derived form of Humanin (SEQ ID NO:3) or a functional fragment thereof where the fragment contains the methionine at position 16 of SEQ ID NO:3.

1 . A method for identifying a Humanin-like compound that binds to Bax, comprising the steps of:
 (a) contacting said Humanin-like compound with said Bax, under conditions suitable to form a complex; and   (b) determining the ability of said Humanin-like compound to bind said Bax.   
     
     
         2 . The method of  claim 1 , wherein said contacting is performed in vitro. 
     
     
         3 . The method of  claim 1 , wherein said ability to bind said Bax is determined using a method selected from the group consisting of: a two-hybrid assay, co-immunoprecipitation assay, co-localization assay, scintillation proximity assay (SPA), UV or chemical cross-linking, biomolecular interaction analysis (BIA), mass spectrometry (MS), nuclear magnetic resonance (NMR), and fluorescence polarization assays (FPA). 
     
     
         4 . The method of  claim 3 , wherein said ability to bind said Bax is determined using a yeast two-hybrid assay.