Human analogs of murine deubiquitinating protease

Abstract

The present invention is directed to human analogs of murine hematopoetic-specific, cytokine-inducible deubiquinating proteases (“DUBs”) clustered on chromosomes 4 and 8 and their respective regulatory regions. The nucleotides or proteins encoded thereby my be used in assays to identify inhibitors of human DUBs.

1 . An isolated polynucleotide encoding a human deubiquitinating protease selected from the group consisting of hDUB 4.1a, hDUB 4.1b, hDUB 4.2a, hDUB 4.2b, hDUB 4.3, hDUB 4.4, hDUB 4.5, hDUB 4.6, hDUB 4.7, hDUB 4.8, hDUB 4.9, hDUB 4.10, hDUB 4.11, hDUB 8.1, hDUB 8.2, hDUB 8.3, hDUB 8.5, hDUB 8.6, hDUB 8.7, hDUB 8.8, hDUB 8.9, hDUB 8.10, and hDUB 8.11.  
     
     
         2 . An isolated polypeptide comprising a human deubiquitinating protease selected from the group consisting of hDUB 4.1a, hDUB 4.2a, hDUB 4.2b, hDUB 4.3, hDUB 4.4, hDUB 4.5, hDUB 4.6, hDUB 4.7, hDUB 4.8, hDUB 4.9, hDUB 4.10, hDUB 4.11, hDUB 8.1, hDUB 8.2, hDUB 8.3, hDUB 8.5, hDUB 8.6, hDUB 8.7, hDUB 8.8, hDUB 8.9, hDUB 8.10, and hDUB 8.11.  
     
     
         3 . A method of using a polynucleotide according to  claim 1 , wherein the polynucleotide is used in an assay to identify an inhibitor of a hDUB of  claim 1 .  
     
     
         4 . A method of using a polypeptide according to  claim 2 , wherein the polypeptide is used in an assay to identify an inhibitor of a hDUB of  claim 2 .  
     
     
         5 . A method of reducing inflammation by regulating proinflammatory cytokine signaling, by administering a compound capable of inhibiting a polypeptide according to  claim 2 .  
     
     
         6 . A method of modulating an autoimmune disease by altering cytokine receptor signaling involved in lymphocytes proliferation, by administering a compound capable of inhibiting a polypeptide according to  claim 2 .  
     
     
         7 . A method of modulating an immune reaction during infection, by administering a compound capable of inhibiting a polypeptide according to  claim 2 .  
     
     
         8 . A method of reducing inflammation by regulating proinflammatory cytokine signaling, by administering a compound capable of altering regulation of transcription of a polynucleotide of  claim 1 .  
     
     
         9 . A method of modulating an autoimmune disease by altering cytokine receptor signaling involved in lymphocytes proliferation, by administering a compound capable of altering regulation of transcription of a polynucleotide of  claim 1 .  
     
     
         10 . A method of modulating an immune reaction during infection, by administering a compound capable of altering regulation of transcription of a polynucleotide of  claim 1 .  
     
     
         11 . A method of identifying a modulator of a human deubiquitinating protease, wherein a compound is added to the reporter assay comprising a polynucleotide immediately 5′ to a human deubiquitinating protease selected from the group consisting of hDUB 4.1a, hDUB 4.1b, hDUB 4.2a, hDUB 4.2b, hDUB 4.3, hDUB 4.4, hDUB 4.5, hDUB 4.6, hDUB 4.7, hDUB 4.8, hDUB 4.9, hDUB 4.10, hDUB 4.11, hDUB 8.1, hDUB 8.2, hDUB 8.3, hDUB 8.5, hDUB 8.6, hDUB 8.7, hDUB 8.8, hDUB 8.9, hDUB 8.10, and hDUB 8.11 operatively linked to a reporter gene, and the effect of the compound is determined.