Crystal structure of worm NitFhit reveals that a Nit tetramer binds tow Fhit dimers
AssigneeThomas Jefferson University
InventorsCarlo Croce, Charles Brenner, Yuri Pekarsky
Life of this patent
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Abstract
In invertebrates, Fhit is encoded as a fusion protein with Nit. Outside of invertebrates, Nit homologs are found as separate polypeptides in organisms with Fhit homologs. Therefore, Nit and Fhit are expected to interact physically and function in the same cellular pathway. The structure of the NitFhit fusion protein and interactions between the Nit and Fhit polypeptides are defined. The present invention relates to the identification of small molecules that interact with, and regulate, the Nit protein. The present invention further relates to therapeutic compositions and their uses in regulating Nit activity, thereby modulating cellular proliferation.
Claims40
An isolated nucleic acid, comprising a nucleotide sequence encoding a human Nit2 protein, wherein the nucleotide sequence is a cDNA sequence.
A human Nit2 protein.
An antibody which specifically binds to an epitope of a human Nit2 protein.
An isolated nucleic acid, comprising a nucleotide sequence encoding a mouse Nit2 protein, wherein the nucleotide sequence is a cDNA sequence.
A mouse Nit2 protein.
An antibody which specifically binds to an epitope of a mouse Nit2 protein.
An S. pombe Nit2 protein.
An antibody which specifically binds to an epitope of a S. pombe Nit2 protein.
An S. cerevisiae Nit3 protein.
An antibody which specifically binds to an epitope of a S. cerevisae Nit3 protein.
An isolated nucleic acid, comprising a nucleotide sequence encoding a X. laevis Nit1 protein, wherein the nucleotide sequence is a cDNA sequence.
A X. laevis Nit1 protein.
An antibody which specifically binds to an epitope of a X. laevis Nit1 protein.
A S. pombe Nit1 protein.
An antibody which specifically binds to an epitope of a S. pombe Nit1 protein.
An S. cerevisiae Nit2 protein.
An antibody which specifically binds to an epitope of a S. cerevisiae Nit2 protein.
A method of identifying a molecule that specifically binds to a Nit2 protein and is functionally active in mimicking a Fhit interaction, comprising
- a) contacting said Nit2 with a plurality of molecules under conditions conducive to binding between said Nit2 and said molecules;
- and
- b) identifying a molecule within said plurality of molecules that specifically binds to said Nit2 and is functionally active in mimicking said Fhit interaction.
A compound comprising a Fhit mimic, wherein said mimic binds to a Nit2 protein in any cell and is functionally active in mimicking a Fhit interaction.
A method of treating a disease state in which an activity of a Nit2 protein is altered in a mammal, comprising administering a therapeutically effective amount of a Fhit mimic, wherein said Fhit mimic binds to said Nit2 protein, thereby inducing programmed cell death.
A pharmaceutical composition comprising a Fhit mimic.
A method of identifying a molecule that specifically binds to a Nit2 protein and is functionally active in antagonizing a Fhit interaction, comprising
- a) contacting said Nit2 with a plurality of molecules under conditions conducive to binding between said Nit2 and said molecules;
- and
- b) identifying a molecule within said plurality of molecules that specifically binds to said Nit2 and is functionally active in antagonizing said Fhit interaction.
A compound comprising a Fhit antagonist, wherein said antagonist binds to a Nit2 protein in any cell and is functionally active in antagonizing a Fhit interaction.
A method of treating a disease state in which an activity of a Nit2 protein is altered in a mammal, comprising administering a therapeutically effective amount of a Fhit antagonist, wherein said Fhit antagonist binds to said Nit2 protein, thereby promoting cell proliferation.
A pharmaceutical composition comprising a Fhit antagonist.
Dependencies are inferred from the claim text.