Members of TNF and TNFR families

Abstract

New members of the TNF and the TNFR superfamily of proteins have been identified. These proteins are promising targets for therapeutic intervention and mimesis. TNF-L and TNFR-L proteins can be used to induce cell death and/or proliferation of cells. Members of these superfamilies have been implicated in a broad variety of disease processes, making them central biological and physiological regulators.

1 . An isolated human protein having an amino acid sequence which is at least 85% identical to an amino acid sequence selected from the group consisting of SEQ ID NOS:1, 2, 17, and 20, wherein percent identity is determined using a Smith-Waterman homology search algorithm using an affine gap search with a gap open penalty of 12 and a gap extension penalty of 1.  
     
     
         2 . The isolated human protein of  claim 1  which has an amino acid sequence selected from the group consisting of SEQ ID NOS:1, 2, 17, and 20.  
     
     
         3 . A fusion protein comprising a first protein segment and a second protein segment fused together by means of a peptide bond, wherein the first protein segment consists of a protein having an amino acid sequence selected from the group consisting of SEQ ID NOS:1, 2, and 17.  
     
     
         4 . A preparation of antibodies which specifically bind to a protein having an amino acid sequence selected from the group consisting of SEQ ID NOS:1, 2, 17, and 20.  
     
     
         5 . A cDNA molecule which encodes a protein having an amino acid sequence which is at least 85% identical to an amino acid sequence selected from the group consisting of SEQ ID NOS:1, 2, 17, and 20, wherein percent identity is determined using a Smith-Waterman homology search algorithm using an affine gap search with a gap open penalty of 12 and a gap extension penalty of 1.  
     
     
         6 . The cDNA molecule of  claim 5  which encodes an amino acid sequence selected from the group consisting of SEQ ID NOS:1, 2, 17, and 20.  
     
     
         7 . The cDNA molecule of  claim 6  which comprises a nucleotide sequence selected from the group consisting of SEQ ID NOS:6, 7, 18 and 19.  
     
     
         8 . A cDNA molecule which is at least 85% identical to a nucleotide sequence selected from the group consisting of SEQ ID NOS:6, 7, 18, and 19, wherein percent identity is determined using a Smith-Waterman homology search algorithm using an affine gap search with a gap open penalty of 12 and a gap extension penalty of 1.  
     
     
         9 . An isolated and purified subgenomic polynucleotide comprising a nucleotide sequence which hybridizes to a nucleotide sequence selected from the group consisting of SEQ ID NOS:6, 7, 18, and 19 after washing with 0.2×SSC at 65° C., wherein the nucleotide sequence encodes a protein having an amino acid sequence selected from the group consisting of SEQ ID NOS:1, 2, and 17.  
     
     
         10 . A construct comprising. 
 a promoter; and    a polynucleotide segment encoding an amino acid sequence selected from the group consisting of SEQ ID NOS:1, 2, 17, and 20, wherein the polynucleotide segment is located downstream from the promoter, wherein transcription of the polynucleotide segment initiates at the promoter.    
     
     
         11 . A host cell comprising a construct which comprises: 
 a promoter; and    a polynucleotide segment encoding an amino acid sequence selected from the group consisting of SEQ ID NOS:1, 2, 17, and 20.    
     
     
         12 . A recombinant host cell comprising a new transcription initiation unit, wherein the new transcription initiation unit comprises in 5′ to 3′ order: 
 (a) an exogenous regulatory sequence,  
 (b) an exogenous exon; and  
 (c) a splice donor site, wherein the new transcription initiation unit is located upstream of a coding sequence of a gene, wherein the coding sequence is selected from the group consisting of SEQ ID NOS:6, 7, 18, and 19, wherein the exogenous regulatory sequence controls transcription of the coding sequence of the gene.  
 
     
     
         13 . A method of screening for a compound capable of modulating cell death inducing activity of a protein, comprising the steps of: 
 incubating a first population of cells and a protein in the presence of a test compound, wherein the protein comprises an amino acid sequence selected from the group of amino acid sequences shown in SEQ ID NOS:1-5, 17, and 20;    incubating a second population of cells and the protein in the absence of a test compound; and    determining viability of the first and second populations, wherein a test compound which increases or decreases viability of the first population relative to the second population is identified as capable of modulating the cell death inducing activity of the protein.    
     
     
         14 . The method of  claim 13  wherein the protein is provided to the first and second populations of cells by transfecting the first and second populations of cells with a polynucleotide encoding the protein.  
     
     
         15 . The method of  claim 13  wherein the polynucleotide comprises a nucleotide sequence selected from the group consisting of SEQ ID NOS:6-10, 18, and 19.  
     
     
         16 . A method of identifying a binding partner of a first protein, comprising the steps of: 
 incubating a first protein with a second protein, wherein the first protein comprises an amino acid sequence selected from the group consisting of SEQ ID NO:1-5, 17, and 20;    detecting formation of a complex between the first and second proteins, wherein formation of the complex identifies the second protein as a binding partner of the first protein.