Essential downstream component of the wingless signaling pathway and therapeutic and diagnostic applications based thereon
An isolated polypeptide comprising a peptide which consists of a legless homology domain (HD); wherein the peptide inhibits Lgs function in colon cancer cells; and a composition comprising the same, are disclosed.
1. An isolated polypeptide consisting of:
(i) a Drosophila Legless (dLgs) protein consisting of amino acids 1 to 1464 of SEQ ID NO:23, or
(ii) a peptide fragment of (i), wherein said fragment has the amino acid sequence of SEQ ID NO:2 or SEQ ID NO:4 and inhibits tcf-driven luciferase activity in colon cancer cells, or
(iii) a peptide fragment of (i) having at least 90% amino acid sequence identity to the amino acid sequence of SEQ ID NO:4 and inhibits tcf-driven luciferase activity in colon cancer cells, or
(iv) a peptide having at least 90% amino acid sequence identity to the amino acid sequence of SEQ ID NO:5 and inhibits tcf-driven luciferase activity in colon cancer cells, or
(v) a peptide fragment of (i) having at least 90% amino acid sequence identity to the amino acid sequence of SEQ ID NO:2 and inhibits tcf-driven luciferase activity in colon cancer cells, or
(vi) a peptide fragment of (i) having at least 90% amino acid sequence identity to the amino acid sequence of SEQ ID NO:3 and inhibits tcf-driven luciferase activity in colon cancer cells.
2. A chimeric molecule comprising the polypeptide of claim 1 fused to a heterologous polypeptide.
3. The chimeric molecule according to claim 2 , wherein said heterologous polypeptide is selected from the group consisting of an antigenic epitope, glutathione-S-transferase, thioredoxin, and antibody.
4. A pharmaceutical composition comprising the polypeptide of claim 1 , and a pharmaceutically acceptable carrier.
5. An isolated polypeptide comprising a Drosophila Legless (dLgs) protein comprising amino acids 1 to 1464 of SEQ ID NO:23.
6. The isolated protein as claimed in claim 5 , wherein said protein is encoded by a nucleotide molecule having the nucleotide sequence of SEQ ID NO:1.
7. A chimeric molecule comprising the polypeptide of claim 5 fused to a heterologous polypeptide.
8. The chimeric molecule according to claim 7 , wherein said heterologous polypeptide is selected from the group consisting of an antigenic epitope, glutathione-S-transferase, thioredoxin, and antibody.
9. A pharmaceutical composition comprising the polypeptide of claim 5 , and a pharmaceutically acceptable carrier.