Anti-tumor activities and apoptotic mechanism of ribosome-inactivating proteins

Zeng, Meiqi; Zheng, Manyin; Lu, Desheng; Wang, Jun; Jiang, Wenqi; Sha, Ou

doi:10.1186/s40880-015-0030-x

Cited by 35 publications

(26 citation statements)

References 77 publications

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“…In contrast, total mTOR is highly activated and is responsible for the observed activation of p70S6 kinase. Although this activation usually leads to activation of ribosomal protein S6, we did not observe either upregulation or phosphorylation of S6, in agreement with a previous report [ 73 ]. Finally, upregulation of eEF2 can possibly be correlated with phosphorylation of eEF2 kinase by p70S6K, which leads to its inactivation and allows eEF2 to remain activated and promote translation elongation [ 74 ].…”

Section: Discussionsupporting

confidence: 93%

Contribution of miRNAs, tRNAs and tRFs to Aberrant Signaling and Translation Deregulation in Lung Cancer

Skeparnias

Anastasakis

Grafanaki

et al. 2020

Cancers

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Transcriptomics profiles of miRNAs, tRNAs or tRFs are used as biomarkers, after separate examination of several cancer cell lines, blood samples or biopsies. However, the possible contribution of all three profiles on oncogenic signaling and translation as a net regulatory effect, is under investigation. The present analysis of miRNAs and tRFs from lung cancer biopsies indicated putative targets, which belong to gene networks involved in cell proliferation, transcription and translation regulation. In addition, we observed differential expression of specific tRNAs along with several tRNA-related genes with possible involvement in carcinogenesis. Transfection of lung adenocarcinoma cells with two identified tRFs and subsequent NGS analysis indicated gene targets that mediate signaling and translation regulation. Broader analysis of all major signaling and translation factors in several biopsy specimens revealed a crosstalk between the PI3K/AKT and MAPK pathways and downstream activation of eIF4E and eEF2. Subsequent polysome profile analysis and 48S pre-initiation reconstitution experiments showed increased global translation rates and indicated that aberrant expression patterns of translation initiation factors could contribute to elevated protein synthesis. Overall, our results outline the modulatory effects that possibly correlate the expression of important regulatory non-coding RNAs with aberrant signaling and translation deregulation in lung cancer.

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Section: Discussionsupporting

confidence: 93%

Contribution of miRNAs, tRNAs and tRFs to Aberrant Signaling and Translation Deregulation in Lung Cancer

Skeparnias

Anastasakis

Grafanaki

et al. 2020

Cancers

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“…Limited proteolysis yielded fragments of the RIPs MAP30 and GAP31 that retained full HIV-integrase inhibition and HIV-LTR topological-inactivation activities, as well as tumor cell-growth inhibitory activity at very low concentrations ranging from 0.2 to 0.4 nM but did not retain their ribosome-inactivation activity [ 53 ]. These RIPs display a variety of antimicrobial activities and broad-spectrum antiviral properties against both human and animal pathogens [ 71 ] and understanding their exact mechanisms of action in depth would be beneficial [ 72 ]. It has been stated that as few as one RIP molecule per cell could entirely inhibit protein synthesis [ 33 ].…”

Section: Resultsmentioning

confidence: 99%

Expression of a Recombinant Anti-HIV and Anti-Tumor Protein, MAP30, in Nicotiana tobacum Hairy Roots: A pH-Stable and Thermophilic Antimicrobial Protein

et al. 2016

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In contrast to conventional antibiotics, which microorganisms can readily evade, it is nearly impossible for a microbial strain that is sensitive to antimicrobial proteins to convert to a resistant strain. Therefore, antimicrobial proteins and peptides that are promising alternative candidates for the control of bacterial infections are under investigation. The MAP30 protein of Momordica charantia is a valuable type I ribosome-inactivating protein (RIP) with anti-HIV and anti-tumor activities. Whereas the antimicrobial activity of some type I RIPs has been confirmed, less attention has been paid to the antimicrobial activity of MAP30 produced in a stable, easily handled, and extremely cost-effective protein-expression system. rMAP30-KDEL was expressed in Nicotiana tobacum hairy roots, and its effect on different microorganisms was investigated. Analysis of the extracted total proteins of transgenic hairy roots showed that rMAP30-KDEL was expressed effectively and that this protein exhibited significant antibacterial activity in a dose-dependent manner. rMAP30-KDEL also possessed thermal and pH stability. Bioinformatic analysis of MAP30 and other RIPs regarding their conserved motifs, amino-acid contents, charge, aliphatic index, GRAVY value, and secondary structures demonstrated that these factors accounted for their thermophilicity. Therefore, RIPs such as MAP30 and its derived peptides might have promising applications as food preservatives, and their analysis might provide useful insights into designing clinically applicable antibiotic agents.

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“…Further, we assayed the cytotoxicity of the rMU1-44G4 IT on L929-shCD105+ mouse cells as a reduction of cell viability using the WST-1 reagent rather than inhibition of protein synthesis since viability is more sensitive to inhibitors than translation, most likely due to the pleiotropic cellular effects of RIPs [ 20 , 25 ]. As shown in Figure 4 , rMU1-44G4 IT kills cells with an IC 50 value of 3.9 × 10 −10 M for L929-shCD105+ cells and >10 −7 M for control untransfected L929 cells.…”

Section: Resultsmentioning

confidence: 99%

Anti-Human Endoglin (hCD105) Immunotoxin—Containing Recombinant Single Chain Ribosome-Inactivating Protein Musarmin 1

Barriuso

Antolı́n

Arias

et al. 2016

Toxins

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Endoglin (CD105) is an accessory component of the TGF-β receptor complex, which is expressed in a number of tissues and over-expressed in the endothelial cells of tumor neovasculature. Targeting endoglin with immunotoxins containing type 2 ribosome-inactivating proteins has proved an effective tool to reduce blood supply to B16 mice tumor xenografts. We prepared anti-endoglin immunotoxin (IT)—containing recombinant musarmin 1 (single chain ribosome-inactivating proteins) linked to the mouse anti-human CD105 44G4 mouse monoclonal antibody via N-succinimidyl 3-(2-pyridyldithio) propionate (SPDP). The immunotoxin specifically killed L929 fibroblast mouse cells transfected with the short form of human endoglin with IC50 values in the range of 5 × 10−10 to 10−9 M.

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Anti-tumor activities and apoptotic mechanism of ribosome-inactivating proteins

Cited by 35 publications

References 77 publications

Contribution of miRNAs, tRNAs and tRFs to Aberrant Signaling and Translation Deregulation in Lung Cancer

Contribution of miRNAs, tRNAs and tRFs to Aberrant Signaling and Translation Deregulation in Lung Cancer

Expression of a Recombinant Anti-HIV and Anti-Tumor Protein, MAP30, in Nicotiana tobacum Hairy Roots: A pH-Stable and Thermophilic Antimicrobial Protein

Anti-Human Endoglin (hCD105) Immunotoxin—Containing Recombinant Single Chain Ribosome-Inactivating Protein Musarmin 1

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