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

An isolated nucleic acid molecule encoding a NACHT domain, comprising:

• (a) a nucleic acid molecule encoding the NACHT domain amino acid set forth as any of SEQ ID NOS:107, 110, 113, 116, 119, 122, 125, 128;
• (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 NACHT domain.

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.

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.

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.

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.

An isolated PAAD domain polypeptide, comprising the amino acid sequence set forth as any of SEQ ID NOS:

• 118, 121, 124 or 127.

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.

An isolated NACHT domain polypeptide, comprising an amino acid sequence set forth as any of SEQ ID NOS:107, 110, 113, 116, 119, 122, 125, 128.

An isolated peptide comprising at least 10 contiguous amino acids of any of SEQ ID NOS:70, 72, 74 or 76.

A method of identifying an agent that modulates PAAD domain-mediated inhibition of NFκB activity, comprising the steps of:

• (a) contacting a cell that recombinantly expresses a PAAD domain-containing polypeptide with a candidate agent, wherein said PAAD domain polypeptide comprises 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;
• and
• (b) detecting NFκB activity in said cell, whereas increased or decreased NFκB activity in said cell compared to a control cell indicates that said candidate agent is an agent that modulates PAAD domain-mediated inhibition of NFκB activity.

A method of decreasing expression of a PAAD domain-containing polypeptide in a cell, comprising introducing an antisense or dsRNA nucleic molecule into a cell, wherein said antisense or dsRNA nucleic molecule binds to any of SEQ ID NOS:69, 71, 73 or 75.