Nicola Landi1, Severina Pacifico1, Sara Ragucci1, Rosario Iglesias2, Simona Piccolella1, Adolfo Amici3, Antonella M A Di Giuseppe1, Antimo Di Maro4. 1. Department of Environmental, Biological and Pharmaceutical Sciences and Technologies, University of Campania "Luigi Vanvitelli", I-81100 Caserta, Italy. 2. Department of Biochemistry and Molecular Biology and Physiology, Faculty of Sciences, University of Valladolid, E-47011 Valladolid, Spain. 3. Department of Odontostomatologic and Specialized Clinical Sciences, Polytechnic University of Marche, I-60131 Ancona, Italy. 4. Department of Environmental, Biological and Pharmaceutical Sciences and Technologies, University of Campania "Luigi Vanvitelli", I-81100 Caserta, Italy. Electronic address: antimo.dimaro@unina2.it.
Abstract
BACKGROUND: Several species belonging to Ascomycota phylum produce extracellular ribonucleases, known as ribotoxins, which exhibit RNase activity through the cleavage of a single phosphodiester bond, located at the universally conserved sarcin/ricin loop of the large rRNA leading to inhibition of protein biosynthesis. Clarifying the structure-function relationship in ribotoxins is interesting for their use in human tumour therapy and in construction of pest resistant transgenic plants. RESULTS: The ribotoxin Ageritin has been isolated for the first time from the Basidiomycetes class. The enzyme, characterized by means of its amino acid composition, N-terminal sequence and a circular dichroism, structurally differs from Ascomycota ribotoxin prototype, although it was able, as α-sarcin, to release a specific α-fragment. However, it does not display aspecific ribonucleolytic activity. Ageritin exerts cytotoxicity and cell death promoting effects towards CNS model cell lines (SK-N-BE(2)-C, U-251 and C6), as vinblastine, a plant alkaloid used in cancer therapy. Moreover, our results indicate that Ageritin initially activates caspase-8, whereas caspase-9 cleavage was not detected, demonstrating the involvement of an extrinsic apoptotic pathway. CONCLUSIONS: Our findings show that Ageritin is the earliest diverging member of the Ascomycota ribotoxin family, suggesting that ribotoxins are more widely distributed among fungi than previously believed. GENERAL SIGNIFICANCE: Ageritin, structurally different from the widely known Ascomycota ribotoxins, with promising anti-cancer properties vs. aggressive brain tumours, has been found from the basidiomycete fungus Agrocybe aegerita. Finally, this finding highlights that the ribotoxin family has divergent members in Basidiomycota phylum, whose structural and functional characterization can give new information on ribotoxin or ribonuclease superfamilies.
BACKGROUND: Several species belonging to Ascomycota phylum produce extracellular ribonucleases, known as ribotoxins, which exhibit RNase activity through the cleavage of a single phosphodiester bond, located at the universally conserved sarcin/ricin loop of the large rRNA leading to inhibition of protein biosynthesis. Clarifying the structure-function relationship in ribotoxins is interesting for their use in humantumour therapy and in construction of pest resistant transgenic plants. RESULTS: The ribotoxin Ageritin has been isolated for the first time from the Basidiomycetes class. The enzyme, characterized by means of its amino acid composition, N-terminal sequence and a circular dichroism, structurally differs from Ascomycota ribotoxin prototype, although it was able, as α-sarcin, to release a specific α-fragment. However, it does not display aspecific ribonucleolytic activity. Ageritin exerts cytotoxicity and cell death promoting effects towards CNS model cell lines (SK-N-BE(2)-C, U-251 and C6), as vinblastine, a plant alkaloid used in cancer therapy. Moreover, our results indicate that Ageritin initially activates caspase-8, whereas caspase-9 cleavage was not detected, demonstrating the involvement of an extrinsic apoptotic pathway. CONCLUSIONS: Our findings show that Ageritin is the earliest diverging member of the Ascomycota ribotoxin family, suggesting that ribotoxins are more widely distributed among fungi than previously believed. GENERAL SIGNIFICANCE: Ageritin, structurally different from the widely known Ascomycota ribotoxins, with promising anti-cancer properties vs. aggressive brain tumours, has been found from the basidiomycete fungus Agrocybe aegerita. Finally, this finding highlights that the ribotoxin family has divergent members in Basidiomycota phylum, whose structural and functional characterization can give new information on ribotoxin or ribonuclease superfamilies.
Authors: Annageldi Tayyrov; Sophie Azevedo; Robert Herzog; Eva Vogt; Simon Arzt; Peter Lüthy; Pie Müller; Martin Rühl; Florian Hennicke; Markus Künzler Journal: Appl Environ Microbiol Date: 2019-10-16 Impact factor: 4.792
Authors: Nicola Landi; Sara Ragucci; Lucía Citores; Angela Clemente; Hafiza Z F Hussain; Rosario Iglesias; José M Ferreras; Antimo Di Maro Journal: Toxins (Basel) Date: 2022-08-19 Impact factor: 5.075
Authors: Ilaria Baglivo; Sara Ragucci; Paolo D'Incecco; Nicola Landi; Rosita Russo; Franco Faoro; Paolo V Pedone; Antimo Di Maro Journal: Int J Mol Sci Date: 2020-09-28 Impact factor: 5.923