Methods for treating diabetes mellitus

Abstract

In accordance with the present invention, it has been discovered that CREB binding protein (CBP) cooperates with upstream activators involved in the activation of transcription of such signal dependent transcription factors as c-Jun (responsive to phorbol ester), serum response factor, and the like. It has also been discovered that CBP can be employed in an assay to identify compounds which disrupt the ability of such signal dependent transcription factors to activate transcription. In another aspect, it has been discovered that CBP can be employed in an assay to identify new signal dependent transcription factors. In yet another aspect of the present invention, it has been discovered that CBP can be employed in an assay to identify novel co-factor protein(s) which mediate the interaction between signal dependent transcription factors and inducer molecules involved in the activation of transcription. Accordingly, the present invention provides methods for the identification of compounds which inhibit activation of cAMP and mitogen responsive genes and methods for the identification of novel signal dependent transcription factors and co-factor proteins. In still another aspect, methods employing compounds which inhibit intracellular signal-induced response pathways have been developed for the treatment of diabetes mellitus.

That which is claimed is:  
     
         1 . An isolated nucleic acid comprising a sequence encoding a fragment of CREB binding protein (CBP), wherein said fragment includes all or a portion of CBP which binds to CREB.  
     
     
         2 . The isolated nucleic acid of  claim 1  wherein said fragment includes the arginine residue at position 600 of SEQ ID NO:2  
     
     
         3 . The isolated nucleic acid of  claim 1  wherein said fragment of CBP is 1-661 of SEQ ID NO:2.  
     
     
         4 . The isolated nucleic acid of  claim 1  wherein said fragment of CBP is 461-661 of SEQ ID NO:2.  
     
     
         5 . The isolated nucleic acid of  claim 1  wherein said fragment of CBP is 634-648 of SEQ ID NO:2  
     
     
         6 . An isolated nucleic acid comprising a sequence encoding a mutant fragment of CREB binding protein (CBP), wherein said fragment includes all or a portion of CBP which binds to CREB.  
     
     
         7 . The isolated nucleic acid of  claim 1  wherein said fragment the residue at position 600 of SEQ ID NO:2 is an amino acid other than arginine.  
     
     
         8 . The isolated nucleic acid of  claim 1  wherein said fragment includes the residue at position 600 of SEQ ID NO:2 is glutamine.  
     
     
         9 . A CBP fragment encoded by the sequence of  claim 1 .  
     
     
         10 . An antibody reactive with the CBP fragment of  claim 9.