DADD, death activator death domain protein
AssigneeGenetics Institute, Inc.
InventorsJean-Baptiste Telliez, Lih-Ling Lin
Life of this patent
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Abstract
Polynucleotides encoding DADD protein are also disclosed, along with vectors, host cells, and methods of making DADD protein. Methods of identifying inhibitors of DADD death domain binding and inhibitors identified by such methods are also disclosed.
Claims22
An isolated polynucleotide encoding a protein having DADD protein activity selected from the group consisting of:
- (a) a polynucleotide comprising the nucleotide sequence of SEQ ID NO:
- 12;
- (b) a polynucleotide comprising the nucleotide sequence of SEQ ID NO:
- 12 from nucleotide 794 to nucleotide 3052;
- (c) a polynucleotide comprising the nucleotide sequence of SEQ ID NO:
- 12 from nucleotide 1295 to nucleotide 3052;
- (d) a polynucleotide comprising the nucleotide sequence of SEQ ID NO:
- 12 from nucleotide 2726 to nucleotide 2929;
- (e) a polynucleotide comprising a fragment of the nucleotide sequence of SEQ ID NO:
- 12;
- (f) a polynucleotide encoding a DADD protein comprising the amino acid sequence of SEQ ID NO:
- 13;
- (g) a polynucleotide encoding a DADD protein comprising the amino acid sequence of SEQ ID NO:
- 13 from amino acid 167 to amino acid 753;
- (h) a polynucleotide encoding a DADD protein comprising the amino acid sequence of SEQ ID NO:
- 13 from amino acid 645 to amino acid 712;
- (i) a polynucleotide encoding a DADD protein comprising a fragment of the amino acid sequence of SEQ ID NO:13;
- and
- (j) a polynucleotide capable of hybridizing under stringent conditions to any one of the polynucleotides specified in (a)-(i).
A composition of claim I wherein said polynucleotide is operably linked to an expression control sequence.
A composition comprising a protein having DADD protein activity which comprises an amino acid sequence selected from the group consisting of:
- (a) the amino acid sequence of SEQ ID NO:
- 13;
- (b) the amino acid sequence of SEQ ID NO:
- 13 from amino acid 167 to amino acid 753;
- (c) the amino acid sequence of SEQ ID NO:
- 13 from amino acid 645 to amino acid 712;
- and
- (d) fragments of the amino acid sequence of SEQ ID NO:
- 13;
- said protein being substantially free from other mammalian proteins.
A method of identifying an inhibitor of binding of a DADD protein to a second protein having a death domain which comprise:
- (a) combining said DADD protein with said second protein, said combination forming a first binding mixture;
- (b) measuring the amount of binding between the DADD protein and the second protein in the first binding mixture;
- (c) combining a compound with the DADD protein and the second protein to form a second binding mixture;
- (d) measuring the amount of binding between the DADD protein and the second protein in the second binding mixture;
- and
- (e) comparing the amount of binding in the first binding mixture with the amount of binding in the second binding mixture;
- wherein the compound is capable of inhibiting binding when a decrease in the amount of binding occurs in the second mixture as compared to the first mixture.
A method of identifying an inhibitor of DADD death domain binding are also provided by the present invention which comprise:
- (a) transforming a cell with a first polynucleotide encoding a DADD protein, a second polynucleotide encoding a second protein having a death domain, and at least one reporter gene, wherein the expression of the reporter gene is regulated by the binding of the DADD protein encoded by the first polynucleotide to the second protein encoded by the second polynucleotide;
- (b) growing the cell in the presence of and in the absence of a compound;
- and
- (c) comparing the degree of expression of the reporter gene in the presence of and in the absence of the compound;
- wherein the compound is capable of inhibiting DADD death domain binding when a decrease in the degree of expression of the reporter gene occurs.
Dependencies are inferred from the claim text.