Fungal ribotoxins: molecular dissection of a familyof natural killers



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Lacadena, Javier and Álvarez García, Elisa and Carreras Sangrà, Nelson and Herrero Galán, Elías and Alegre Cebollada, Jorge and García Ortega, Lucía and Oñaderra, Mercedes and Gavilanes, José G. and Martínez del Pozo, Álvaro (2007) Fungal ribotoxins: molecular dissection of a familyof natural killers. FEMS Microbiology Reviews, 31 . pp. 212-237. ISSN 0168-6445

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RNase T1 is the best known representative of a large family of ribonucleolytic
proteins secreted by fungi, mostly Aspergillus and Penicillium species. Ribotoxins
stand out among them by their cytotoxic character. They exert their toxic action by
first entering the cells and then cleaving a single phosphodiester bond located
within a universally conserved sequence of the large rRNA gene, known as the
sarcin–ricin loop. This cleavage leads to inhibition of protein biosynthesis,
followed by cellular death by apoptosis. Although no protein receptor has been
found for ribotoxins, they preferentially kill cells showing altered membrane
permeability, such as those that are infected with virus or transformed. Many steps
of the cytotoxic process have been elucidated at the molecular level by means of a
variety of methodological approaches and the construction and purification of
different mutant versions of these ribotoxins. Ribotoxins have been used for the
construction of immunotoxins, because of their cytotoxicity. Besides this activity,
Aspf1, a ribotoxin produced by Aspergillus fumigatus, has been shown to be one of
the major allergens involved in allergic aspergillosis-related pathologies. Protein
engineering and peptide synthesis have been used in order to understand the basis
of these pathogenic mechanisms as well as to produce hypoallergenic proteins with
potential diagnostic and immunotherapeutic applications.

Item Type:Article
Uncontrolled Keywords:Aspf1; Filamentous fungi; Immunotoxin; RNase; Sarcin
Subjects:Sciences > Chemistry > Molecular biology
Sciences > Chemistry > Biochemistry
Medical sciences > Biology > Biotechnology
ID Code:6883
Deposited On:11 Dec 2007
Last Modified:06 Feb 2014 07:52

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