PAAD domain-containing polypeptides, encoding nucleic acids, and methods of use

Abstract

The invention provides isolated nucleic acid molecules encoding PAAD-domain containing polypeptides and functional fragments thereof, including fragments containing PAAD domains, NACHT domains and ARED domains, encoded polypeptides, and antibodies. Also provided are methods of identifying polypeptides and agents that associate with a PAAD-domain containing polypeptide or fragment thereof, or that alter an association of a PAAD domain-containing polypeptides. Further provided are methods of identifying agents that modulate PAAD domain-mediated inhibition of NFκB activity, or modulate an activity of a NACHT domain of a PAAD domain-containing polypeptide. Also provided are methods of modulating NFκB transcriptional activity in a cell, and methods of altering expression of a PAAD domain-containing polypeptide in a cell.

1 . An isolated nucleic acid molecule encoding a PAAD-containing polypeptide, comprising:
 (a) a nucleic acid molecule encoding a polypeptide comprising the amino acid sequence set forth as SEQ ID NOs: 66, 68, 70, 72, 74, 76 or 84; or   (b) a nucleic acid molecule that hybridizes to the complement of the nucleic acid molecule of (a) under highly stringent conditions, where the nucleic acid molecule encodes a biologically active PAAD domain-containing polypeptide.   
     
     
         2 . The nucleic acid molecule of  claim 1 , encoding SEQ ID NO: 66, 68, 70, 72, 74, 76 or 84. 
     
     
         3 . A vector containing the nucleic acid molecule of  claim 1 . 
     
     
         4 . A recombinant cell containing the nucleic acid molecule of  claim 1 . 
     
     
         5 . An isolated nucleic acid molecule encoding a PAAD domain, comprising:
 (a) a nucleic acid molecule encoding a PAAD domain amino acid sequence set forth as any of SEQ ID NOS: 118, 121, 124 or 127; or   (b) a nucleic acid molecule that hybridizes to the nucleic acid molecule of (a) under highly stringent conditions, where the nucleic acid molecule encodes a biologically active PAAD domain.   
     
     
         6 . A vector containing the nucleic acid molecule of  claim 5 . 
     
     
         7 . A recombinant cell containing the nucleic acid molecule of  claim 5 . 
     
     
         8 - 10 . (canceled) 
     
     
         11 . An oligonucleotide comprising at least 17 nucleotides capable of specifically hybridizing with the nucleotide sequence set forth in any of SEQ ID NOS:69, 71, 73 or 75 or the complement thereof. 
     
     
         12 . An oligonucleotide comprising at least 50 nucleotides capable of specifically hybridizing with the nucleotide sequence set forth in any of SEQ ID NOS:69, 71, 73 or 75 or the complement thereof. 
     
     
         13 . An isolated PAAD domain-containing polypeptide, comprising an amino acid sequence at least 80% identical to the amino acid sequence set forth in any of SEQ ID NOS:66, 68, 70, 72, 74, 76 or 84, wherein said polypeptide is a biologically active PAAD domain-containing polypeptide. 
     
     
         14 . The PAAD domain-containing polypeptide of  claim 13 , wherein said polypeptide comprises the amino acid sequence set forth as any of SEQ ID NOS:66, 68, 70, 72, 74, 76 or 84. 
     
     
         15 . An isolated PAAD domain polypeptide, comprising an amino acid sequence at least 80% identical to the amino acid sequence set forth as any of SEQ ID NOS: 118, 121, 124 or 127, wherein said polypeptide is a biologically active PAAD domain polypeptide. 
     
     
         16 . (canceled) 
     
     
         17 . An isolated NACHT domain polypeptide, comprising an amino acid sequence at least 80% identical to the amino acid sequence set forth as any of SEQ ID NOS:107, 110, 113, 116, 119, 122, 125, 128, wherein said polypeptide is a biologically active NACHT domain polypeptide. 
     
     
         18 - 20 . (canceled) 
     
     
         21 . An isolated anti-PAAD antibody having specific reactivity with the PAAD domain-containing polypeptide of  claim 14 . 
     
     
         22 . The antibody of  claim 21 , wherein said antibody is a monoclonal antibody. 
     
     
         23 . A cell line producing the monoclonal antibody of  claim 22 . 
     
     
         24 . The antibody of  claim 21 , wherein said antibody is a polyclonal antibody. 
     
     
         25 - 40 . (canceled)