Inhibition of cell growth by a fused protein of human ribonuclease 1 and human basic fibroblast growth factor

Junichiro Futami, Masaharu Seno, Masakazu Ueda, Hiroko Tada, Hidenori Yamada

Research output: Contribution to journalArticle

38 Citations (Scopus)

Abstract

Pancreatic-type RNases are considered to have cytotoxic potential due to their ability to degrade RNA molecules when they enter the cytosol. However, most of these RNases show little cytotoxicity because cells have no active uptake mechanism for these RNases and because the ubiquitous cytoplasmic RNase inhibitor is considered to play a protective role against the endocytotic leak of RNases from the outside of cells. To study the cytotoxic potential of RNase toward malignant cells targeting growth factor receptors, the C-terminus of human RNase 1 was fused to the N-terminus of human basic fibroblast growth factor (bFGF). This RNase-FGF fused protein effectively inhibited the growth of mouse melanoma cell line B16/BL6 with high levels of cell surface FGF receptor. This effect appeared to result from prolongation of the overall cell cycle rather than the killing of cells or specific arrest in a particular phase of the cell cycle. Thus, human RNase 1 fused to a ligand of cell surface molecules, such as the FGF receptor, is shown to be an effective candidate for a selective cell targeting agent with low toxic effects on normal cell types.

Original languageEnglish
Pages (from-to)1013-1019
Number of pages7
JournalProtein Engineering
Volume12
Issue number11
Publication statusPublished - 1999

Fingerprint

Cell growth
Fibroblast Growth Factor 2
Fibroblasts
Ribonucleases
Proteins
Growth
Cells
Fibroblast Growth Factor Receptors
Cell Cycle
Pancreatic Ribonuclease
Molecules
Growth Factor Receptors
human STK36 protein
Intercellular Signaling Peptides and Proteins
Poisons
Cell Surface Receptors
Cytotoxicity
Cytosol
RNA
Melanoma

Keywords

  • Cytotoxic
  • FGF
  • Immunotoxin
  • RNase
  • Targeting

ASJC Scopus subject areas

  • Molecular Biology
  • Biochemistry

Cite this

Inhibition of cell growth by a fused protein of human ribonuclease 1 and human basic fibroblast growth factor. / Futami, Junichiro; Seno, Masaharu; Ueda, Masakazu; Tada, Hiroko; Yamada, Hidenori.

In: Protein Engineering, Vol. 12, No. 11, 1999, p. 1013-1019.

Research output: Contribution to journalArticle

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