Plant Ribosome-Inactivating Proteins: Progesses, Challenges and Biotechnological Applications (and a Few Digressions)

Fabbrini, Maria Serena; Katayama, M.; Nakase, Ikuhiko; Vago, Riccardo

doi:10.3390/toxins9100314

Cited by 59 publications

(62 citation statements)

References 189 publications

(244 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Fig. 2; Fabbrini et al 2017). Higher protein sequence identities and homologies are found when comparing ricin and mistletoe lectin (ML-I) from Viscum album (Suppl.…”

Section: Ricin (Ricin D Rca-ii Rca60)mentioning

confidence: 96%

Ricin and Ricinus communis in pharmacology and toxicology-from ancient use and “Papyrus Ebers” to modern perspectives and “poisonous plant of the year 2018”

Franke

Scholl

Aigner

2019

Naunyn-Schmiedeberg's Arch Pharmacol

View full text Add to dashboard Cite

While probably originating from Africa, the plant Ricinus communis is found nowadays around the world, grown for industrial use as a source of castor oil production, wildly sprouting in many regions, or used as ornamental plant. As regards its pharmacological utility, a variety of medical purposes of selected parts of the plant, e.g., as a laxative, an anti-infective, or an antiinflammatory drug, have been described already in the sixteenth century BC in the famous Papyrus Ebers (treasured in the Library of the University of Leipzig). Quite in contrast, on the toxicological side, the native plant has become the "poisonous plant 2018" in Germany. As of today, a number of isolated components of the plant/seeds have been characterized, including, e.g., castor oil, ricin, Ricinus communis agglutinin, ricinin, nudiflorin, and several allergenic compounds. This review mainly focuses on the most toxic protein, ricin D, classified as a type 2 ribosome-inactivating protein (RIP2). Ricin is one of the most potent and lethal substances known. It has been considered as an important bioweapon (categorized as a Category B agent (second-highest priority)) and an attractive agent for bioterroristic activities. On the other hand, ricin presents great potential, e.g., as an anticancer agent or in cell-based research, and is even explored in the context of nanoparticle formulations in tumor therapy. This review provides a comprehensive overview of the pharmacology and toxicology-related body of knowledge on ricin. Toxicokinetic/toxicodynamic aspects of ricin poisoning and possibilities for analytical detection and therapeutic use are summarized as well.

show abstract

“…Fig. 2; Fabbrini et al 2017). Higher protein sequence identities and homologies are found when comparing ricin and mistletoe lectin (ML-I) from Viscum album (Suppl.…”

Section: Ricin (Ricin D Rca-ii Rca60)mentioning

confidence: 96%

Ricin and Ricinus communis in pharmacology and toxicology-from ancient use and “Papyrus Ebers” to modern perspectives and “poisonous plant of the year 2018”

Franke

Scholl

Aigner

2019

Naunyn-Schmiedeberg's Arch Pharmacol

View full text Add to dashboard Cite

show abstract

“…inhibitor of E. coli RNA polymerase (Sheppard et al, 2011). namely conserved tyrosine and tryptophan residues that form the "N-glycosidase signature" (Fabbrini et al, 2017).…”

Section: Structural Similarity Of Csep0064/bec1054 To Rnases and Ripsmentioning

confidence: 99%

A fungal ribonuclease-like effector protein inhibits plant host ribosomal RNA degradation

Pennington

Jones

Kwon³

et al. 2018

Preprint

View full text Add to dashboard Cite

KEY WORDSBlumeria graminis; effector protein; CSEP0064/BEC1054; RIP; Bimolecular Fluorescence Complementation; split YFP; RALPH; RNA-binding protein; RNase structure; powdery mildew Fungal RNase-like effector function -2 RALPH RNase-like proteins expressed in haustoria RFP red fluorescent protein RIP ribosome-inactivating protein RNase ribonuclease rRNA ribosomal RNA SRL sarcin-ricin loop Y2H yeast two-hybrid Fungal RNase-like effector function -3 3 ABSTRACT The biotrophic fungal pathogen Blumeria graminis causes the powdery mildew disease of cereals and grasses. Proteins with a predicted ribonuclease (RNase)-like fold (termed RALPHs) comprise the largest set of secreted effector candidates within the B. graminis f. sp. hordei genome. Their exceptional abundance suggests they play crucial functions during pathogenesis. We show that transgenic expression of RALPH CSEP0064/BEC1054 increases susceptibility to infection in monocotyledenous and dicotyledonous plants. CSEP0064/BEC1054 interacts in planta with five host proteins: two translation elongation factors (eEF1α and eEF1γ), two pathogenesis-related proteins (PR5 and PR10) and a glutathione-S-transferase.We present the first crystal structure of a RALPH, CSEP0064/BEC1054, demonstrating it has an RNase-like fold. The protein interacts with total RNA and weakly with DNA. Methyl jasmonate levels modulate susceptibility to aniline-induced host RNA fragmentation. In planta expression of CSEP0064/BEC1054 reduces the formation of this RNA fragment. We propose that CSEP0064/BEC1054 is a pseudoenzyme that binds to host ribosomes, thereby inhibiting the action of plant ribosome-inactivating proteins that would otherwise lead to host cell death, an unviable interaction and demise of the fungus.

show abstract

“…RIPs can penetrate to the cell by firstly binding to membrane receptors, then passing through the cell membrane by endocytosis and eventually passing in the cytoplasm through shifting from endocytic compartments [2]. Recently, RIPs gain biologists' attention in the biomedical research area because of their diverse activities toward plant and animal cells, including their anticancer, antiviral, antifungal, abortifacient, and antiparasitic effects [2][3][4][5].…”

Section: Introductionmentioning

confidence: 99%

Ribosome-Inactivating Protein α-Momorcharin Derived from Edible Plant Momordica charantia Induces Inflammatory Responses by Activating the NF-kappaB and JNK Pathways

Chen

Zhu

et al. 2019

Toxins

View full text Add to dashboard Cite

Alpha-momorcharin (α-MMC), a member of the ribosome-inactivating protein (RIP) family, has been found in the seeds of Momordica charantia (bitter melon). α-MMC contributes a number of pharmacological activities; however, its inflammatory properties have not been well studied. Here, we aim to determine the inflammatory responses induced by recombinant α-MMC and identify the underlying mechanisms using cell culture and animal models. Recombinant α-MMC was generated in Rosetta™(DE3)pLysS and purified by the way of nitrilotriacetic acid (NTA) chromatography. Treatment of recombinant α-MMC at 40 μg/mL exerted sub-lethal cytotoxic effect on THP-1 monocytic cells. Transcriptional profiling revealed that various genes coding for cytokines and other proinflammatory proteins were upregulated upon recombinant α-MMC treatment in THP-1 cells, including MCP-1, IL-8, IL-1β, and TNF-α. Recombinant α-MMC was shown to activate IKK/NF-κB and JNK pathways and the α-MMC-induced inflammatory gene expression could be blocked by IKKβ and JNK inhibitors. Furthermore, murine inflammatory models further demonstrated that α-MMC induced inflammatory responses in vivo. We conclude that α-MMC stimulates inflammatory responses in human monocytes by activating of IKK/NF-κB and JNK pathways, raising the possibility that consumption of α-MMC-containing food may lead to inflammatory-related diseases.

show abstract

Plant Ribosome-Inactivating Proteins: Progesses, Challenges and Biotechnological Applications (and a Few Digressions)

Cited by 59 publications

References 189 publications

Ricin and Ricinus communis in pharmacology and toxicology-from ancient use and “Papyrus Ebers” to modern perspectives and “poisonous plant of the year 2018”

Ricin and Ricinus communis in pharmacology and toxicology-from ancient use and “Papyrus Ebers” to modern perspectives and “poisonous plant of the year 2018”

A fungal ribonuclease-like effector protein inhibits plant host ribosomal RNA degradation

Ribosome-Inactivating Protein α-Momorcharin Derived from Edible Plant Momordica charantia Induces Inflammatory Responses by Activating the NF-kappaB and JNK Pathways

Contact Info

Product

Resources

About