Apo-2LI and Apo-3 polypeptides

Abstract

Novel polypeptides, designated Apo-3 and Apo-2L1, involved in apoptosis are provided. Compositions including chimeric molecules, nucleic acids, and antibodies are also provided.

1 . Isolated biologically active Apo-2LI having at least about 80% sequence identity with native sequence Apo-2LI having amino acid residues 1 to 181 of SEQ ID NO:1. 
     
     
         2 . The Apo-2LI of  claim 1  wherein said Apo-2LI has at least about 90% sequence identity. 
     
     
         3 . The Apo-2LI of  claim 2  wherein said Apo-2LI has at least about 95% sequence identity. 
     
     
         4 . Isolated Apo-2LI comprising amino acid residues 1 to 181 of SEQ ID NO:1. 
     
     
         5 . A chimeric molecule comprising the Apo-2LI of  claim 1  or  claim 4  fused to a heterologous amino acid sequence. 
     
     
         6 . The chimeric molecule of  claim 5  wherein said heterologous amino acid sequence is an epitope tag sequence. 
     
     
         7 . The chimeric molecule of  claim 5  wherein said heterologous amino acid sequence is an immunoglobulin sequence. 
     
     
         8 . The chimeric molecule of  claim 7  wherein said immunoglobulin sequence is an IgG. 
     
     
         9 . A dimer molecule comprising a first Apo-2LI and a second Apo-2LI. 
     
     
         10 . An antibody which binds to Apo-2LI. 
     
     
         11 . The antibody of  claim 10  wherein said antibody is a monoclonal antibody. 
     
     
         12 . Isolated nucleic acid encoding Apo-2LI. 
     
     
         13 . The nucleic acid of  claim 12  wherein said nucleic acid encodes an Apo-2LI comprising amino acid residues 1 to 181 of SEQ ID NO:1. 
     
     
         14 . A vector comprising the nucleic acid of  claim 12 . 
     
     
         15 . A host cell comprising the vector of  claim 14 . 
     
     
         16 . A method of producing Apo-2LI comprising culturing the host cell of  claim 15  and recovering the Apo-2LI from the host cell culture. 
     
     
         17 . An article of manufacture, comprising:
 a container;   a label on said container; and   a composition contained within said container, said composition comprising Apo-2LI.   
     
     
         18 . The article of manufacture of  claim 17  further comprising instructions for using the Apo-2LI in vivo or ex vivo. 
     
     
         19 . Isolated biologically active Apo-3 polypeptide having at least about 80% sequence identity with native sequence Apo-3 having amino acid residues 1 to 417 of SEQ ID NO:6. 
     
     
         20 . The Apo-3 of  claim 19  wherein said Apo-3 has at least about 90% sequence identity. 
     
     
         21 . The Apo-3 of  claim 20  wherein said Apo-3 has at least about 95% sequence identity. 
     
     
         22 . Isolated native sequence Apo-3 comprising amino acid residues 1 to 417 of SEQ ID NO:6. 
     
     
         23 . Isolated biologically active polypeptide having at least about 80% sequence identity with the extracellular domain sequence of Apo-3 having amino acid residues 1 to 198 of SEQ ID NO:6. 
     
     
         24 . The polypeptide of  claim 23  wherein said polypeptide has at least about 90% sequence identity. 
     
     
         25 . The polypeptide of  claim 24  wherein said polypeptide is Apo-2LI. 
     
     
         26 . Isolated extracellular domain sequence of Apo-3 comprising amino acid residues 1 to 198 of SEQ ID NO:6. 
     
     
         27 . Isolated death domain sequence of Apo-3 comprising amino acid residues 338 to 417 of SEQ ID NO:6. 
     
     
         28 . A chimeric molecule comprising the Apo-3 of  claim 22  or the extracellular domain sequence of  claim 23  fused to a heterologous amino acid sequence. 
     
     
         29 . The chimeric molecule of  claim 28  wherein said heterologous amino acid sequence is an epitope tag sequence. 
     
     
         30 . The chimeric molecule of  claim 28  wherein said heterologous amino acid sequence is an immunoglobulin sequence. 
     
     
         31 . The chimeric molecule of  claim 30  wherein said immunoglobulin sequence is an IgG. 
     
     
         32 . An antibody which binds to Apo-3 or to the extracellular domain sequence of  claim 23 . 
     
     
         33 . The antibody of  claim 32  wherein said antibody is a monoclonal antibody. 
     
     
         34 . Isolated nucleic acid encoding the Apo-3 of  claim 22 , the extracellular domain sequence of  claim 23  or the death domain sequence of  claim 27 . 
     
     
         35 . The nucleic acid of  claim 34  wherein said nucleic acid encodes native sequence Apo-3 comprising amino acid residues 1 to 417 of SEQ ID NO:6. 
     
     
         36 . A vector comprising the nucleic acid of  claim 34 . 
     
     
         37 . The vector of  claim 36  operably linked to control sequences recognized by a host cell transformed with the vector. 
     
     
         38 . A host cell comprising the vector of  claim 36 . 
     
     
         39 . A process of using a nucleic acid molecule encoding Apo-3 to effect production of Apo-3 comprising culturing the host cell of  claim 38 . 
     
     
         40 . A non-human, transgenic animal which contains cells that express nucleic acid encoding Apo-3. 
     
     
         41 . The animal of  claim 40  which is a mouse or rat. 
     
     
         42 . A non-human, knockout animal which contains cells having an altered gene encoding Apo-3. 
     
     
         43 . The animal of  claim 42  which is a mouse or rat. 
     
     
         44 . An article of manufacture, comprising a container and a composition contained within said container, wherein the composition includes Apo-3 polypeptide or Apo-3 antibodies. 
     
     
         45 . The article of manufacture of  claim 44  further comprising instructions for using the Apo-3 polypeptide or antibodies in vivo or ex vivo.