Tumor necrosis factor related ligand

1. A substantially pure nucleic acid comprising a sequence encoding a polypeptide comprising amino acids 36 to 284 of SEQ ID NO:4.

2. A substantially pure nucleic acid comprising a sequence encoding a polypeptide that comprises an amino terminal truncation of SEQ ID NO:4, the amino terminal truncation consisting essentially of amino acids 36 to 284 of SEQ ID NO:4.

3. A substantially pure nucleic acid comprising a sequence encoding a polypeptide, wherein said nucleic acid hybridizes under high stringency conditions to the complement of a coding sequence, wherein the stringent conditions comprise washing steps using 2×SSC, 0.1% SDS at 65° C., wherein said polypeptide is capable of inducing apoptosis in an HT-29 colon carcinoma cell, and wherein said coding sequence is selected from the group consisting of:

(a) nucleotides 106 to 852 of SEQ ID NO: 3; and

(b) nucleotides 241 to 852 of SEQ ID NO: 3.

4. A substantially pure nucleic acid comprising a sequence that encodes the polypeptide of SEQ ID NO:4, or a soluble fragment thereof that is capable of binding to an HT-29 colon carcinoma cell and inducing apoptosis in said carcinoma cell.

5. The nucleic acid according to claim 4 , wherein said sequence encodes a soluble fragment of the polypeptide of SEQ ID NO:4, wherein the N-terminus of the soluble fragment is at any one of amino acids 81 to 139 of SEQ ID NO:4.

6. The nucleic acid according to any one of claims 1 , 2 , 5 , 3 , or 4 , wherein said polypeptide or said soluble fragment thereof is fused to an amino acid tag sequence.

7. The nucleic acid according to any one of claims 1 , 2 , 5 , 3 , or 4 , wherein the encoded polypeptide or said soluble fragment thereof is fused to a type I or type II leader sequence.

8. The nucleic acid according to any one of claims 1 , 2 , 5 , 3 , or 4 , operably linked to an expression control sequence.

9. An isolated host cell transformed with the nucleic acid according to any one of claims 1 , 2 , 5 , 3 , or 4 .

10. The host cell according to claim 9 , wherein said host cell is a mammalian cell.

11. The host cell according to claim 10 , wherein said mammalian cell is a human cell.

12. A method of producing a substantially pure polypeptide comprising the steps of:

(a) culturing the transformed host cell according to claim 9 and;

(b) isolating said polypeptide produced by said host cell to obtain the substantially pure polypeptide.

13. A method of producing a polypeptide in an animal cell culture comprising the steps of:

(a) introducing into said cell culture a vector comprising the nucleic acid according to any one of claims 1 , 2 , 5 , 3 , or 4 and;

(b) allowing said cell culture to live under conditions wherein said nucleic acid is expressed in said cell culture to produce the polypeptide, thereby providing an expressed polypeptide.

14. The method according to claim 13 , wherein said animal cell culture is an insect cell culture or a mammalian cell culture.

15. The method according to claim 13 , wherein said vector is a virus or a plasmid.

16. A method of expressing a polypeptide in an animal cell culture comprising the steps of:

(a) introducing into said cell culture a vector comprising a nucleic acid encoding the polypeptide of SEQ ID NO:4, or a soluble fragment thereof that is capable of binding to a HT-29 colon carcinoma cell and inducing apoptosis in said carcinoma cell, and

(b) allowing said cell culture to live under conditions wherein said nucleic acid is expressed in said cell culture, thereby providing an expressed polypeptide.

17. The method according to claim 16 , wherein said animal cell culture is an insect cell culture or a mammalian cell culture.

18. The method according to claim 16 , wherein said vector is a virus or a plasmid.

19. A substantially pure nucleic acid comprising a sequence that encodes a polypeptide that comprises the amino acid sequence of SEQ ID NO:4.

20. A substantially pure nucleic acid comprising a sequence encoding a polypeptide, said sequence consisting essentially of SEQ ID NO:3.

21. A substantially pure nucleic acid comprising a sequence that encodes a polypeptide consisting essentially of SEQ ID NO:4.

22. A substantially pure nucleic acid comprising a sequence encoding a polypeptide, said sequence comprising SEQ ID NO:3.

23. The nucleic acid according to claim 19 , 20 , 21 or 22 , operably linked to an expression control sequence.

24. An isolated host cell transformed with the nucleic acid according to claim 23 .

25. A method for producing a substantially pure polypeptide encoded by a nucleic acid sequence that comprises SEQ ID NO:3, the method comprising:

culturing the host cell according to claim 24 ; and

isolating a polypeptide encoded by the nucleic acid sequence that comprises SEQ ID NO:3 produced by said transformed host cell to obtain the substantially pure polypeptide encoded by the nucleic acid sequence that comprises SEQ ID NO:3.

26. A method of expressing a polypeptide in an animal cell culture comprising the steps of:

introducing into said cell culture a vector comprising the nucleic acid of claim 19 , 20 , 21 or 22 ; and

allowing said cell culture to live under conditions wherein said nucleic acid is expressed in said cell culture, thereby providing an expressed polypeptide.

27. The method according to claim 26 , wherein said animal cell culture is an insect cell culture or a mammalian cell culture.

28. The method according to claim 26 , wherein said vector is a virus or a plasmid.

29. A substantially pure nucleic acid comprising a sequence that encodes a fragment of SEQ ID NO:4, wherein said fragment of SEQ ID NO:4 is capable of binding to an HT-29 colon carcinoma cell and inducing apoptosis in said carcinoma cell and comprises amino acids 81 to 284 of SEQ ID NO:4.

30. The method according to claim 26 , wherein said cell culture is a human cell culture.

31. The host cell according to claim 24 , wherein said host cell is a mammalian cell.

32. The host cell according to claim 31 , wherein said mammalian cell is a human cell.

33. A substantially pure nucleic acid that comprises a sequence that encodes a polypeptide consisting essentially of a soluble fragment of SEQ ID NO:4 that is capable of binding to an HT-29 colon carcinoma cell and inducing apoptosis in said HT-29 colon carcinoma cell.

34. A nucleic acid vector that comprises the nucleic acid of claim 1 , 2 , 5 , 3 , or 4 .

35. A method of producing a polypeptide in an isolated host cell, the method comprising:

(a) providing an isolated host cell that contains a vector comprising the nucleic acid of claim 1 , 2 , 5 , 3 or 4 and;

(b) maintaining the isolated host cell under conditions wherein the nucleic acid is expressed, to thereby produce the polypeptide in the isolated host cell.

36. The method of claim 35 wherein the host cell is prokaryotic.

37. The method of claim 36 further comprising isolating said polypeptide produced by said host cell to obtain a substantially pure polypeptide.

38. The method of claim 35 wherein the host cell is eukaryotic.

39. The method of claim 38 further comprising isolating said polypeptide produced by said host cell to obtain a substantially pure polypeptide.

40. The method of claim 12 wherein the host cell is prokaryotic.

41. The method of claim 12 wherein the host cell is eukaryotic.

42. The method of claim 13 further comprising isolating said polypeptide produced by said host cell to obtain a substantially pure polypeptide.

43. The nucleic acid of claim 3 , wherein said coding sequence is (a) nucleotides 106 to 852 of SEQ ID NO: 3.

44. A substantially pure nucleic acid comprising a sequence that encodes a soluble fragment of the amino acid sequence of SEQ ID NO:4 having one amino acid substitution, wherein the soluble fragment is capable of binding to an HT-29 colon carcinoma cell and inducing apoptosis in said carcinoma cell.

45. The nucleic acid of claim 44 wherein the amino acid substitution is a conservative substitution.