Abstract
Basic fibroblast growth factor (bFGF) was inserted in the middle of human ribonuclease 1 (RNase1) sequence at an RNase inhibitor (RI)-binding site (Gly89) by a new gene fusion technique, insertional-fusion. The resultant insertional-fusion protein (CL-RFN89) was active both as bFGF and as RNase. Furthermore, it acquired an additional ability of evading RI through steric blockade of RI-binding caused by fused bFGF domain. As a result, CL-RFN89 showed stronger growth inhibition on B16/BL6 melanoma cells than an RI-sensitive tandem fusion protein. Thus, the insertional-fusion technique increases accessible positions for gene fusion on RNase, resulting in construction of a potent cytotoxic RNase.
| Original language | English |
|---|---|
| Pages (from-to) | 39-43 |
| Number of pages | 5 |
| Journal | FEBS Letters |
| Volume | 568 |
| Issue number | 1-3 |
| DOIs | |
| Publication status | Published - Jun 18 2004 |
Keywords
- Basic fibroblast growth factor
- CL-RNase1, 4-118 cross-linked RNase1 mutant
- Insertional-fusion protein
- Protein engineering
- RFNs, insertional-fusion proteins between hRNase1 and bFGF
- Ribonuclease
- Targeting
- bFGF, basic fibroblast growth factor
ASJC Scopus subject areas
- Biophysics
- Structural Biology
- Biochemistry
- Molecular Biology
- Genetics
- Cell Biology
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Cite this
Tada, H., Onizuka, M., Muraki, K., Masuzawa, W., Futami, J., Kosaka, M., Seno, M., & Yamada, H. (2004). Insertional-fusion of basic fibroblast growth factor endowed ribonuclease 1 with enhanced cytotoxicity by steric blockade of inhibitor interaction. FEBS Letters, 568(1-3), 39-43. https://doi.org/10.1016/j.febslet.2004.05.007