The ribonucleolytic activity of the ribotoxin α-sarcin is not essential for in vitro protein biosynthesis inhibition

Álvarez-García, Elisa; Diago-Navarro, Elizabeth; Herrero-Galán, Elías; Garcı́a-Ortega, Lucı́a; López-Villarejo, Juan; Olmo, Nieves; Dı́az-Orejas, Ramón; Gavilanes, José G.; Martínez‐del‐Pozo, Álvaro

doi:10.1016/j.bbapap.2011.06.017

Cited by 5 publications

(5 citation statements)

References 41 publications

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“…Finally, besides the toxicity exerted by ribotoxins due to their catalytically inactivation of the ribosome, there are some studies highlighting the ability of α-sarcin to inhibit protein biosynthesis and promote cytotoxicity independently of its ribonucleolytic activity [ 48 , 49 ]. These observations suggest an alternative mechanism for cell death that still needs to be explored.…”

Section: Fungal Ribotoxinsmentioning

confidence: 99%

Fungal Ribotoxins: A Review of Potential Biotechnological Applications

Olombrada

Lázaro-Gorines

López-Rodríguez

et al. 2017

Toxins

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Fungi establish a complex network of biological interactions with other organisms in nature. In many cases, these involve the production of toxins for survival or colonization purposes. Among these toxins, ribotoxins stand out as promising candidates for their use in biotechnological applications. They constitute a group of highly specific extracellular ribonucleases that target a universally conserved sequence of RNA in the ribosome, the sarcin-ricin loop. The detailed molecular study of this family of toxic proteins over the past decades has highlighted their potential in applied research. Remarkable examples would be the recent studies in the field of cancer research with promising results involving ribotoxin-based immunotoxins. On the other hand, some ribotoxin-producer fungi have already been studied in the control of insect pests. The recent role of ribotoxins as insecticides could allow their employment in formulas and even as baculovirus-based biopesticides. Moreover, considering the important role of their target in the ribosome, they can be used as tools to study how ribosome biogenesis is regulated and, eventually, may contribute to a better understanding of some ribosomopathies.

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Section: Fungal Ribotoxinsmentioning

confidence: 99%

Fungal Ribotoxins: A Review of Potential Biotechnological Applications

Olombrada

Lázaro-Gorines

López-Rodríguez

et al. 2017

Toxins

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“…Similarly, an α -sarcin mutant that could not inhibit protein synthesis was cytotoxic (Alford et al 2009). These results provide evidence that RIPs and ribotoxins can promote cell death by a mechanism that is independent of depurination or cleavage of the SRL (Alford et al 2009; Alvarez-Garcia et al 2011; Hudak et al 2004; Li et al 2007; Di et al 2011). Understanding ribosome interactions of RIPs and how they affect toxicity at the molecular level is important not only for developing antidotes, but also for understanding ribosome function.…”

Section: Discussionmentioning

confidence: 73%

“…The EF2 can protect ribosomes from RTA (Fernandez-Puentes et al 1976) and block binding of RTA to the ribosome (Cawley et al 1979). More recent studies indicated that a catalytically inactive α -sarcin mutant, which could not cleave the SRL was able to inhibit protein synthesis possibly by binding to the ribosomes (Alvarez-Garcia et al 2011). These results indicated that site-specific damage to the SRL may not account entirely for the activity of RIPs and ribotoxins.…”

Section: Discussionmentioning

confidence: 99%

Interaction of Ricin and Shiga Toxins with Ribosomes

Tumer

2011

Current Topics in Microbiology and Immunology

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Ricin and Shiga toxins designated as ribosome inactivating proteins (RIPs) are RNA N-glycosidases that depurinate a specific adenine (A4324 in rat 28S rRNA) in the conserved α-sarcin/ricin loop of the large rRNA, inhibiting protein synthesis. Evidence obtained from a number of studies suggests that interaction with ribosomal proteins plays an important role in the catalytic activity and ribosome specificity of RIPs. This review summarizes the recent developments in identification of the ribosomal proteins that interact with ricin and Shiga toxins and the principles governing these interactions.

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“…Previous studies showed that α-sarcin killed rhabdomyosarcoma cells via apoptosis and suggested that α-sarcin-induced caspase activation is a pathway downstream of the 28S rRNA catalytic cleavage . However, there have been some studies showing the ability of α-sarcin to inhibit protein biosynthesis and promote cell death independently of its rRNA cleavage activity and JNK activation. , Therefore, alternative cell death mechanisms besides protein synthesis inhibition could also be involved in Ageritin toxicity.…”

Section: Resultsmentioning

confidence: 99%

“…38 However, there have been some studies showing the ability of α-sarcin to inhibit protein biosynthesis and promote cell death independently of its rRNA cleavage activity and JNK activation. 46,47 Therefore, alternative cell death mechanisms besides protein synthesis inhibition could also be involved in Ageritin toxicity.…”

mentioning

confidence: 99%

Ageritin, a Ribotoxin from Poplar Mushroom (Agrocybe aegerita) with Defensive and Antiproliferative Activities

et al. 2019

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Ribotoxins make up a group of extracellular rRNA endoribonucleases produced by ascomycetes that display cytotoxicity toward animal cells, having been proposed as insecticidal agents. Recently, the ribotoxin Ageritin has been isolated from the basidiomycetes Agrocybe aegerita (poplar mushroom), suggesting that ribotoxins are widely distributed among fungi. To gain insights into the protective properties of Ageritin against pathogens and its putative biotechnological applications, we have tested several biological activities of Ageritin, comparing them with those of the well-known ribotoxin α-sarcin, and we found that Ageritin displayed, in addition to the already reported activities, (i) antibacterial activity against Micrococcus lysodeikticus, (ii) activity against the tobacco mosaic virus RNA, (iii) endonuclease activity against a supercoiled plasmid, (iv) nuclease activity against genomic DNA, (v) cytotoxicity to COLO 320, HeLa, and Raji cells by promoting apoptosis, and (vi) antifungal activity against the green mold Penicillium digitatum. Therefore, Ageritin and α-sarcin can induce resistance not only to insects but also to viruses, bacteria, and fungi. The multiple biological activities of Ageritin could be exploited to improve resistance to different pathogens by engineering transgenic plants. Furthermore, the induction of cell death by different mechanisms turns these ribotoxins into useful tools for cancer therapy.

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The ribonucleolytic activity of the ribotoxin α-sarcin is not essential for in vitro protein biosynthesis inhibition

Cited by 5 publications

References 41 publications

Fungal Ribotoxins: A Review of Potential Biotechnological Applications

Fungal Ribotoxins: A Review of Potential Biotechnological Applications

Interaction of Ricin and Shiga Toxins with Ribosomes

Ageritin, a Ribotoxin from Poplar Mushroom (Agrocybe aegerita) with Defensive and Antiproliferative Activities

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