Polypeptide inhibitors of SMAD3 polypeptide activities
This document provides polypeptide inhibitors of Smad3 polypeptide activities. For example, methods and materials for using polypeptides (e.g., polypeptides designed to include both a cell penetrating amino acid sequence and an amino acid segment of a SH3 domain of a SNX9 polypeptide) to inhibit one or more Smad3 polypeptide activities are provided. This document also provides methods and materials for using RNA interference to treat a disease (e.g., a fibrotic disease) in a mammal (e.g., a human).
1. A nucleic acid molecule encoding a polypeptide comprising a cell penetrating amino acid sequence and an amino acid segment of a SH3 domain of a sorting nexin 9 (SNX9) polypeptide, wherein said amino acid segment is less than 45 amino acid residues in length and comprises the amino acid sequence set forth in SEQ ID NO:6 or 7.
2. The nucleic acid molecule of claim 1 , wherein said cell penetrating amino acid sequence comprises the amino acid sequence set forth in SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, or SEQ ID NO:5.
3. The nucleic acid molecule of claim 1 , wherein said cell penetrating amino acid sequence comprises GYGRKKRRQRRRGS (SEQ ID NO:37).
4. The nucleic acid molecule of claim 1 , wherein said polypeptide comprises the amino acid sequence set forth in any one of SEQ ID NOs:9, 11, 13-16, 18, 19, 21, 22, 24, and 25.
5. The nucleic acid molecule of claim 1 , wherein said amino acid segment comprises the amino acid sequence set forth in SEQ ID NO:6.
6. The nucleic acid molecule of claim 1 , wherein said amino acid segment comprises the amino acid sequence set forth in SEQ ID NO:7.
7. A host cell comprising a nucleic acid molecule encoding a polypeptide comprising a cell penetrating amino acid sequence and an amino acid segment of a SH3 domain of a sorting nexin 9 (SNX9) polypeptide, wherein said amino acid segment is less than 45 amino acid residues in length and comprises the amino acid sequence set forth in SEQ ID NO:6 or 7.
8. The host cell of claim 7 , wherein said cell penetrating amino acid sequence comprises the amino acid sequence set forth in SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, or SEQ ID NO:5.
9. The host cell of claim 7 , wherein said cell penetrating amino acid sequence comprises GYGRKKRRQRRRGS (SEQ ID NO:37).
10. The host cell of claim 7 , wherein said polypeptide comprises the amino acid sequence set forth in any one of SEQ ID NOs:9, 11, 13-16, 18, 19, 21, 22, 24, and 25.
11. The host cell of claim 7 , wherein said amino acid segment comprises the amino acid sequence set forth in SEQ ID NO:6.
12. The host cell of claim 7 , wherein said amino acid segment comprises the amino acid sequence set forth in SEQ ID NO:7.