Novel molecules of the tnf ligand superfamily and uses therefor
OwnerSamantha J. Busfieldinventor
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Abstract
Novel TRASH polypeptides, proteins, and nucleic acid molecules are disclosed. In addition to isolated, full-length TRASH proteins, the invention further provides isolated TRASH fusion proteins, antigenic peptides and anti-TRASH antibodies. The invention also provides TRASH nucleic acid molecules, recombinant expression vectors containing a nucleic acid molecule of the invention, host cells into which the expression vectors have been introduced and non-human transgenic animals in which a TRASH gene has been introduced or disrupted. Diagnostic, screening and therapeutic methods utilizing compositions of the invention are also provided.
Claims61
An isolated nucleic acid molecule which encodes a TRASH protein, comprising a nucleotide sequence at least about 60% homologous to a nucleotide sequence of SEQ ID NO:3, or a complement thereof.
An isolated nucleic acid molecule which encodes a TRASH protein, comprising a nucleotide sequence at least about 60% homologous to a nucleotide sequence of SEQ ID NO:1, SEQ ID NO:6, SEQ ID NO:8, SEQ ID NO:10, or a complement thereof.
An isolated nucleic acid molecule comprising a nucleotide sequence encoding a protein which comprises an amino acid sequence at least about 60% homologous to the amino acid sequence of SEQ ID NO:2, SEQ ID NO:7, SEQ ID NO:9, or SEQ ID NO:11.
An isolated nucleic acid molecule encoding a TRASH protein, comprising a nucleotide sequence which hybridizes under stringent hybridization conditions to a nucleic acid molecule comprising the nucleotide sequence of SEQ ID NO:3, SEQ ID NO:6, SEQ ID NO:8, or SEQ ID NO:10.
An isolated nucleic acid molecule encoding a TRASH protein, comprising a nucleotide sequence which hybridizes under stringent hybridization conditions to a nucleic acid molecule comprising the nucleotide sequence of SEQ ID NO:1.
An isolated nucleic acid molecule comprising a nucleotide sequence which hybridizes under stringent hybridization conditions to a nucleic acid molecule comprising nucleotides 1-1025 of SEQ ID NO:1.
An isolated nucleic acid molecule comprising a nucleotide sequence which hybridizes under stringent hybridization conditions to a nucleic acid molecule comprising nucleotides 273-1344 of SEQ ID NO:1.
An isolated nucleic acid molecule at least 500 nucleotides in length which hybridizes under stringent hybridization conditions to a nucleic acid molecule comprising the nucleotide sequence of SEQ ID NO:1, SEQ ID NO:3, SEQ ID NO:6, SEQ ID NO:8, or SEQ ID NO:10.
A nonhuman transgenic animal which contains cells carrying a transgene encoding TRASH protein.
A nonhuman homologous recombinant animal which contains cells having an altered TRASH gene.
An isolated TRASH protein comprising an amino acid sequence at least about 60% homologous to the amino acid sequence of SEQ ID NO:2, SEQ ID NO:7, SEQ ID NO:9, or SEQ ID NO:11.
An isolated TRASH protein which is encoded by a nucleic acid molecule comprising a nucleotide sequence at least about 60% homologous to a nucleotide sequence of SEQ ID NO:3, SEQ ID NO:6, SEQ ID NO:8, SEQ ID NO:10 or a complement thereof.
An isolated TRASH protein which is encoded by a nucleic acid molecule comprising a nucleotide sequence at least about 60% homologous to a nucleotide sequence of SEQ ID NO:1, SEQ ID NO:3, SEQ ID NO:6, SEQ ID NO:8, SEQ ID NO:10, or a complement thereof.
An isolated TRASH protein which is encoded by a nucleic acid molecule comprising a nucleotide sequence which hybridizes under stringent hybridization conditions to a nucleic acid molecule comprising the nucleotide sequence of SEQ ID NO:1, SEQ ID NO:3, SEQ ID NO:6, SEQ ID NO:8, or SEQ ID NO:10.
An isolated protein comprising an amino acid sequence sufficiently homologous to the amino acid sequence of SEQ ID NO:2, SEQ ID NO:7, SEQ ID NO:9, or SEQ ID NO:11, wherein the protein retains a TRASH biological activity.
An isolated protein comprising the amino acid sequence of SEQ ID NO:2, SEQ ID NO:7, SEQ ID NO:9, or SEQ ID NO:11.
A fusion protein comprising a TRASH polypeptide operatively linked to a non-TRASH polypeptide.
An antibody that specifically binds TRASH.
A method for modulating a cell-associated activity comprising contacting a cell with an agent which modulates TRASH protein activity or TRASH nucleic acid expression such that the cell-associated activity is altered relative to the cell-associated activity of the cell in the absence of the agent.
A method for treating a subject having a disorder characterized by aberrant TRASH protein activity or nucleic acid expression comprising administering to the subject a TRASH modulator such that treatment of the subject occurs.
A method for detecting the presence of TRASH activity in a biological sample comprising contacting a biological sample with an agent capable of detecting an indicator of TRASH activity such that the presence of TRASH activity is detected in the biological sample.
A kit for detecting the presence of TRASH activity in a biological sample comprising an agent capable of detecting an indicator of TRASH activity in a biological sample.
A diagnostic assay for identifying a genetic alteration in a cell sample, the presence or absence of the genetic alteration characterized by at least one of (i) aberrant modification or mutation of a gene encoding a TRASH protein, and (ii) mis-regulation of said gene or (iii) aberrant post-translational modification of a TRASH protein.
A method for identifying a compound that modulates the activity of a TRASH protein, comprising:
- a. providing a indicator composition comprising a protein having TRASH activity;
- b. contacting the indicator composition with a test compound;
- and
- c. determining the effect of the test compound on TRASH activity in the indicator composition to thereby identify a compound that modulates the activity of a TRASH protein.
Dependencies are inferred from the claim text.