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A role for the intersubunit disulfides of seminal RNase in the mechanism of its antitumor action by Aurora Bracale; Francesco Castaldi; Lucio Nitsch; Giuseppe D'Alessio is a Biochemistry, Genetics and Molecular Biology article available to read on EtoBox.

What is A role for the intersubunit disulfides of seminal RNase in the mechanism of its antitumor action about?

The dimeric structure of seminal ribonuclease (BS‐RNase) is maintained by noncovalent interactions and by two intersubunit disulfide bridges. Another unusual feature of this enzyme is its antitumour action, consisting in a cytotoxic activity selective for malignant cells. This cytotoxic action is exerted when the protein reaches the cytosol of the affected cells, where it degrades ribosomal RNA, thus blocking protein synthesis and leading cells to death. The current model proposed for the mechanism of antitumour action of BS‐RNase is based on the ability of the protein to resist the neutralizing action of the cytosolic RNase inhibitor, a resistance due to the dimeric structure of the enzyme. Monomeric RNases, and monomeric derivatives of BS‐RNase, are strongly bound by the inhibitor and inactive as antitumor agents. Here we report on monomeric derivatives of BS‐RNase that, although strongly inhibited by the cytosolic RNase inhibitor, are cytotoxic towards malignant cells. These monomers are produced by reductive cleavage of the intersubunit disulfides of the native, dimeric protein followed by linking the exposed sulfhydryls to small thiols through formation of mixed disulfides. We

Who reads A role for the intersubunit disulfides of seminal RNase in the mechanism of its antitumor action?

Author

Aurora Bracale; Francesco Castaldi; Lucio Nitsch; Giuseppe D'Alessio

Publisher

John Wiley and Sons; Springer; Wiley (Blackwell Publishing); Springer-Verlag; Blackwell Publishing Inc.; Springer Verlag; Wiley; Springer Science and Business Media LLC (ISSN 1432-1327)

Published

2003

Language

EN

Field

Biochemistry, Genetics and Molecular Biology (Physical Sciences)