Signal transduction protein TAB2
View Patent ↗A novel signal transducer TAB2 which acts as an adapter molecule of TRAF6 and TAK1 and mediates the activation of TAK1 in the signal transduction of IL-1 was isolated. TAB2 induced the activation of NF-κB and JNK by IL-1. The signal transduction by IL-1 was inhibited by inhibiting the signal transduction of TAB2 with the use of a dominant negative mutant of TAB2. A compound inhibiting the signal transduction in TAB2 is useful as an anti-inflammatory drug.
1. An isolated polypeptide comprising the amino acid sequence of SEQ ID NO:2 (TAB2).
2. The isolated polypeptide of claim 1 , wherein the polypeptide is a fusion protein comprising SEQ ID NO:2.
3. The isolated polypeptide of claim 2 , wherein the fusion protein comprises a peptide or protein selected from the group consisting of FLAG, 6×His, 10×His, glutathione-S-transferase, influenza agglutinin, immunoglobulin constant region, β galactosidase, and maltose-binding protein.
4. The isolated polypeptide of claim 1 , wherein the polypeptide is a fusion protein comprising the sequence of an immunoglobulin constant region or a maltose-binding protein.
5. An isolated polypeptide comprising a sequence at least 90% identical to SEQ ID NO:2, wherein the polypeptide binds to one or both of TAK1 and TRAF6.
6. The isolated polypeptide of claim 5 , wherein the polypeptide comprises a sequence at least 95% identical to SEQ ID NO:2.
7. The isolated polypeptide of claim 5 , wherein the polypeptide comprises a sequence at least 98% identical to SEQ ID NO:2.
8. The isolated polypeptide of claim 5 , wherein the polypeptide is a fusion protein comprising the sequence of an immunoglobulin constant region or a maltose-binding protein.
9. The isolated polypeptide of claim 5 , wherein the polypeptide comprises an amphipathic α-helix and/or an amino acid sequence corresponding to residues 535-609 of SEQ ID NO:2.
10. An isolated polypeptide that comprises SEQ ID NO:2 or a variant thereof in which up to 10 amino acids are substituted, deleted, and/or inserted in SEQ ID NO:2, wherein said polypeptide binds to one or both of TAK1 and TRAF6.
11. The isolated polypeptide of claim 10 , wherein up to 5 amino acids are substituted, deleted, and/or inserted in SEQ ID NO:2.
12. The isolated polypeptide of claim 10 , wherein up to 3 amino acids are substituted, deleted, and/or inserted in SEQ ID NO:2.
13. The isolated polypeptide of claim 10 , wherein the polypeptide comprises an amphipathic α-helix and/or an amino acid sequence corresponding to residues 535-609 of SEQ ID NO:2.
14. An isolated polypeptide comprising amino acids 1-400 of SEQ ID NO:2 (TAB2N).
15. A pharmaceutical composition comprising, as an active ingredient, the isolated polypeptide of claim 14 .
16. A method of treating a subject having a condition associated with interleukin-1 (IL-1) inflammation, the method comprising administering to the subject a therapeutically effective amount of the composition of claim 15 .
17. The isolated polypeptide of claim 14 , wherein the polypeptide is a fusion protein comprising the sequence of an immunoglobulin constant region or a maltose-binding protein.
18. An isolated polypeptide consisting of the amino acid sequence of SEQ ID NO:2 (TAB2).
19. An isolated polypeptide consisting of amino acids 1-400 of SEQ ID NO:2 (TAB2N).
20. An isolated polypeptide consisting of amino acids 401-693 of SEQ ID NO:2 (TAB2C).
21. A pharmaceutical composition comprising, as an active ingredient, the isolated polypeptide of claim 20 .
22. A method of treating a subject having a condition associated with IL-1 mediated inflammation, the method comprising administering to the subject a therapeutically effective amount of the composition of claim 21 .
23. An isolated polypeptide comprising a sequence at least 90% identical to SEQ ID NO:2, wherein the polypeptide mediates IL-1 signal transduction.
24. An isolated polypeptide comprising a sequence at least 90% identical to SEQ ID NO:2, wherein the polypeptide inhibits IL-1 signal transduction.
25. An isolated polypeptide that comprises SEQ ID NO:2 or a variant thereof in which up to 10 amino acids are substituted in SEQ ID NO:2, wherein said polypeptide mediates IL-1 signaling.
26. An isolated polypeptide that comprises SEQ ID NO:2 or a variant thereof in which up to 10 amino acids are substituted, deleted, and/or inserted in SEQ ID NO:2, wherein said polypeptide inhibits IL-1 signal transduction.