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Intracellular route and mechanism of action of ERB‐hRNase, a human anti‐ErbB2 anticancer immunoagent
Author(s) -
De Lorenzo Claudia,
Di Malta Chiara,
Calì Gaetano,
Troise Fulvia,
Nitsch Lucio,
D’Alessio Giuseppe
Publication year - 2007
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2006.12.034
Subject(s) - cytosol , intracellular , rnase p , mechanism of action , microbiology and biotechnology , in vitro , endosome , chemistry , apoptosis , in vivo , cytotoxic t cell , biochemistry , biology , enzyme , rna , gene
Human anti‐ErbB2 immunoRNase with Erbicin fused to HP‐RNase (ERB‐hRNase) is a fully human immunoRNase made up of human pancreatic RNase fused to a human anti‐ErbB2 scFv. It binds selectively with high affinity to ErbB2‐positive cells, and specifically inhibits their proliferation, in vitro and in vivo. An investigation of its mechanism of action and its intracellular destination has revealed that ERB‐hRNase depends on its RNase activity for cytotoxic action; it reaches the cytosol directly from the endosomal compartment; it is inhibited by the cytosolic RNase inhibitor (cRI), but the levels that ERB‐hRNase reaches in the cytosol neutralize cRI, thus inducing cell death by apoptosis.