title: Cytotoxic activity of chimeric protein PD-L4UWSCI(tr) does not appear be affected by specificity of inhibition mediated by anti-protease WSCI domain.
abstract: In a previously study, a type 1 ribosome inactivating protein (PD-L4) and a wheat subtilisin/chymotrypsin inhibitor (WSCI) were engineered into a chimeric protein (PD-L4UWSCI) that presented in addition to the same properties of both domains an intriguing selective cytotoxic action on murine tumor cells. This finding supported the idea that the protection of C-terminal region of PD-L4 could amplify its cytotoxic action by virtue of a greater resistance to proteases. Several authors indeed revealed that the cytotoxicity of RIPs depends not only on the intracellular routing, but also on the intrinsic resistance to proteolysis. In this regard in the present work we have produced a variant of chimeric protein, named PD-L4UWSCI(tr), changing the inhibitory specificity of WSCI domain. The purpose of this approach was to check if the cytotoxicity of the chimeric protein was altered depending on the properties of protease inhibitor domain or by a different fold of whole protein. Data collected supposedly indicate that WSCI domain contributes to cytotoxicity of chimeric protein exclusively from a structural point of view.
authors.forename: Valeria
authors.initials: V
authors.lastname: Sgambati
authors.forename: Elio
authors.initials: E
authors.lastname: Pizzo
authors.forename: Maria C
authors.initials: MC
authors.lastname: Mezzacapo
authors.forename: Antonella M A
authors.initials: AM
authors.lastname: Di Giuseppe
authors.forename: Nicola
authors.initials: N
authors.lastname: Landi
authors.forename: Elia
authors.initials: E
authors.lastname: Poerio
authors.forename: Antimo
authors.initials: A
authors.lastname: Di Maro
mesh_terms: D016475:3T3 Cells / Q000187:drug effects; D000818:Animals; D003001:Cloning, Molecular; D003603:Cytotoxins / Q000494:pharmacology; D051379:Mice; D008958:Models, Molecular; D010940:Plant Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D015202:Protein Engineering / Q000379:methods; D017434:Protein Structure, Tertiary; D011817:Rabbits; D011993:Recombinant Fusion Proteins / Q000737:chemistry* / Q000235:genetics / Q000494:pharmacology*; D054789:Ribosome Inactivating Proteins, Type 1 / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D014361:Trypsin Inhibitors / Q000737:chemistry* / Q000494:pharmacology
chemical_list: D003603:Cytotoxins; D010940:Plant Proteins; D011993:Recombinant Fusion Proteins; D054789:Ribosome Inactivating Proteins, Type 1; D014361:Trypsin Inhibitors; C504099:WSCI protein, Triticum