Polynucleotides and polypeptides associated with the NF-kB pathway
OwnerJulie Carman, Steven Nadler +1inventors
InventorsJulie Carman, Steven Nadler, John N. Feder
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Abstract
The present invention provides polynucleotides encoding NF-kB-associated polypeptides, fragments and homologues thereof. Also provided are vectors, host cells, antibodies, and recombinant and synthetic methods for producing said polypeptides. The invention further relates to diagnostic and therapeutic methods for applying these NF-kB-associated polypeptides to the diagnosis, treatment, and/or prevention of various diseases and/or disorders related to these polypeptides. The invention further relates to screening methods for identifying agonists and antagonists of the polynucleotides and polypeptides of the present invention.
Claims20
An isolated nucleic acid molecule consisting of a polynucleotide having a nucleotide sequence selected from the group consisting of:
- (a) a polynucleotide fragment of SEQ ID NO:1-108, 125, 127, 132-140, 158-159, or 264-284;
- (b) a polynucleotide encoding a polypeptide fragment of SEQ ID NO:109-118, 126, 128, 144-152, or 160-161, which is hybridizable to SEQ ID NO:1-108, 125, 127, 132-140, 158-159, or 264-284;
- (c) a polynucleotide encoding a polypeptide domain of SEQ ID NO:109-118, 126, 128, 144-152, or 160-161 which is hybridizable to SEQ ID NO:1-108, 125, 127, 132-140, 158-159, or 264-284;
- (d) a polynucleotide encoding a polypeptide epitope of SEQ ID NO:109-118, 126, 128, 144-152, or 160-161, which is hybridizable to SEQ ID NO:1-108, 125, 127, 132-140, 158-159, or 264-284;
- (e) a polynucleotide encoding a polypeptide of SEQ ID NO:109-118, 126, 128, 144-152, or 160-161 which is hybridizable to SEQ ID NO:1-108, 125, 127, 132-140, 158-159, or 264-284, having NFkB modulating activity;
- (f) a polynucleotide which is a variant of SEQ ID NO:1-108, 125, 127, 132-140, 158-159, or 264-284;
- (g) a polynucleotide which is an allelic variant of SEQ ID NO:1-108, 125, 127, 132-140, 158-159, or 264-284;
- (h) a polynucleotide which encodes a species homologue of the SEQ ID NO:109-118, 126, 128, 144-152, or 160-161;
- (i) a polynucleotide which represents the complimentary sequence (antisense) of SEQ ID NO:1-108, 125, 127, 132-140, 158-159, or 264-284;
- (j) a polynucleotide capable of hybridizing under stringent conditions to any one of the polynucleotides specified in (a)-(i), wherein said polynucleotide does not hybridize under stringent conditions to a nucleic acid molecule having a nucleotide sequence of only A residues or of only T residues.
An isolated polypeptide consisting an amino acid sequence selected from the group consisting of:
- (a) a polypeptide fragment of SEQ ID NO:109-118, 126, 128, 144-152, or 160-161;
- (b) a polypeptide fragment of SEQ ID NO:109-118, 126, 128, 144-152, or 160-161, capable of modulating an NFkB response;
- (c) a polypeptide domain of SEQ ID NO:109-118, 126, 128, 144-152, or 160-161;
- (d) a polypeptide epitope of SEQ ID NO:109-118, 126, 128, 144-152, or 160-161;
- (e) a full length protein of SEQ ID NO:109-118, 126, 128, 144-152, or 160-161;
- (f) a variant of SEQ ID NO:109-118, 126, 128, 144-152, or 160-161;
- (g) an allelic variant of SEQ ID NO:109-118, 126, 128, 144-152, or 160-161;
- and
- (h) a species homologue of SEQ ID NO:109-118, 126, 128, 144-152, or 160-161.
A method of identifying a compound that modulates the biological activity of a NFkB associated molecule, comprising:
- (a) combining a candidate modulator compound with a NFkB associated molecule having the sequence set forth in a member of the group consisting of SEQ ID NO:109-118, 126, 128, 144-152, or 160-161, or a polypeptide encoded by a polynucleotide selected from the group consisting of SEQ ID NO:1-108, 125, 127, 132-140, 158-159, or 264-284;
- and
- (b) measuring an effect of the candidate modulator compound on the activity of the NFkB associated molecule.
A method of identifying a compound that modulates the biological activity of an NFkB associated molecule, comprising:
- (a) combining a candidate modulator compound with a host cell expressing a NFkB associated molecule having the sequence as set forth in a member of the group consisting of SEQ ID NO:109-118, 126, 128, 144-152, or 160-161, or a polypeptide encoded by a polynucleotide selected from the group consisting of SEQ ID NO:1-108, 125, 127, 132-140, 158-159, or 264-284;
- and
- (b) measuring an effect of the candidate modulator compound on the activity of the expressed NFkB associated molecule.
A method of identifying a compound that modulates the biological activity of a NFkB associated molecule, comprising:
- (a) combining a candidate modulator compound with a host cell containing a vector comprising the polynucleotide sequence selected from the group consisting of SEQ ID NO:1-108, 125, 127, 132-140, 158-159, or 264-284, wherein a NFkB associated molecule is expressed by the cell;
- and
- (b) measuring an effect of the candidate modulator compound on the activity of the expressed NFkB associated molecule.
A method of screening for a compound that is capable of modulating the biological activity of a NFkB associated molecule, comprising the steps of:
- (a) providing a host cell containing a vector comprising the polynucleotide sequence selected from the group consisting of SEQ ID NO:1-108, 125, 127, 132-140, 158-159, or 264-284;
- (b) determining the biological activity of the NFkB associated molecule in the absence of a modulator compound;
- (c) contacting the cell with the modulator compound;
- and
- (d) determining the biological activity of the NFkB associated molecule in the presence of the modulator compound;
- wherein a difference between the activity of the NFkB associated molecule in the presence of the modulator compound and in the absence of the modulator compound indicates a modulating effect of the compound.
Dependencies are inferred from the claim text.