Ribosome inactivating proteins and apoptosis

Narayanan, Sriram; Surendranath, Kalpana; Bora, Namrata; Surolia, Avadhesha; Karande, Anjali A.

doi:10.1016/j.febslet.2005.01.038

Cited by 137 publications

(105 citation statements)

References 51 publications

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“…The action mechanism of RIPs have been extremely imperceptible and numerous accounts have been put forth to decipher the same. It was earlier believed that the mortality of cells treated with RIPs or RIP-immunotoxins was a result of protein synthesis inhibition alone with subsequent cellular necrosis, however, a stark similarity between RIP treated cells and cells undergoing apoptosis or programmed cell death (PCD) has been observed [17][18][19][20][21] . Jatropha curcas is a well-known and mass cultivated multipurpose plant with immense medicinal value [22][23][24] .…”

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confidence: 99%

Cytological and Subcellular Response of Cells Exposed to the Type-1 RIP Curcin and its Hemocompatibility Analysis

Mohamed

Veeranarayanan

Minegishi

et al. 2014

Sci Rep

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Curcin, a type 1 ribosome inactivating protein (RIP) is investigated here for its cellular competence on six mammalian cell lines. Cells exposed to curcin (100 mg/ml) for 72 h exhibited significant cellular metabolic arrest, with the cancer cell lines being more sensitive. The viability assessment of the cancer cells in a 3D cell culture based assay revealed highly restricted sprouting and proliferation with near to complete dead cell population. Prominent mitochondrial dysfunction, elevated reactive oxygen species levels, nuclear degeneration, structural/mechanical destabilization and suppression of defense mechanisms were imminent with the RIP treated cells. Expression levels of nuclear factor kB (NF-kB), cytoskeletal focal adhesion kinases (FAK) and vinculin were significantly diminished. Vital cellular organelles as nucleus, mitochondria and actin were severely incapacitated on RIP exposure resulting in multimodal apoptosis and necrosis. The ability of curcin to impart comprehensive shutdown of the cells, especially cancer cells, complemented with its hemocompatibility, opens up possibilities of utilizing this ribotoxin as a prospective therapeutic candidate against cancers of diverse origins.

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confidence: 99%

Cytological and Subcellular Response of Cells Exposed to the Type-1 RIP Curcin and its Hemocompatibility Analysis

Mohamed

Veeranarayanan

Minegishi

et al. 2014

Sci Rep

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“…There is evidence that ricin induces apoptosis in a wide variety of animal cells by mechanisms other than protein synthesis inhibition (32). Ricin-induced apoptosis in HeLa cells was associated with oxidative stress, glutathione depletion, and activation of the caspase 3 cascade, followed by downstream events leading to apoptotic cell death (32,39).…”

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confidence: 99%

Ribosome Depurination Is Not Sufficient for Ricin-Mediated Cell Death in Saccharomyces cerevisiae

Baricevic

Saidasan

et al. 2007

Infect Immun

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The plant toxin ricin is one of the most potent and lethal substances known. Ricin inhibits protein synthesis by removing a specific adenine from the highly conserved ␣-sarcin/ricin loop in the large rRNA. Very little is known about how ricin interacts with ribosomes and the molecular mechanism by which it kills cells. To gain insight to the mechanism of ricin-induced cell death, we set up yeast (Saccharomyces cerevisiae) as a simple and genetically tractable system to isolate mutants defective in cytotoxicity. Ribosomes were depurinated in yeast cells expressing the precursor form of the A chain of ricin (pre-RTA), and these cells displayed apoptotic markers such as nuclear fragmentation, chromatin condensation, and accumulation of reactive oxygen species. We conducted a large-scale mutagenesis of pre-RTA and isolated a panel of nontoxic RTA mutants based on their inability to kill yeast cells. Several nontoxic RTA mutants depurinated ribosomes and inhibited translation to the same extent as wild-type RTA in vivo. The mutant proteins isolated from yeast depurinated ribosomes in vitro, indicating that they were catalytically active. However, cells expressing these mutants did not display hallmarks of apoptosis. These results provide the first evidence that the ability to depurinate ribosomes and inhibit translation does not always correlate with ricin-mediated cell death, indicating that ribosome depurination and translation inhibition do not account entirely for the cytotoxicity of ricin.

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“…Other proteins, such as the ribosome inhibitory proteins (RIPs), directly bind the ribosome and irreversibly cleave ribosomal RNA, leading to inhibition of all translation 23 . Thus far, no cellular regulatory protein able to directly bind the ribosome and lead to the selective expression of specific cap-independent messages has been reported.…”

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confidence: 99%

Direct ribosomal binding by a cellular inhibitor of translation

Colón-Ramos

Shenvi

Weitzel

et al. 2006

Nat Struct Mol Biol

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During apoptosis and under conditions of cellular stress, several signaling pathways promote inhibition of cap-dependent translation while allowing continued translation of specific messenger RNAs encoding regulatory and stress-response proteins. We report here that the apoptotic regulator Reaper inhibits protein synthesis by binding directly to the 40S ribosomal subunit. This interaction does not affect either ribosomal association of initiation factors or formation of 43S or 48S complexes. Rather, it interferes with late initiation events upstream of 60S subunit joining, apparently modulating start-codon recognition during scanning. CrPV IRES-driven translation, involving direct ribosomal recruitment to the start site, is relatively insensitive to Reaper. Thus, Reaper is the first known cellular ribosomal binding factor with the potential to allow selective translation of mRNAs initiating at alternative start codons or from certain IRES elements. This function of Reaper may modulate gene expression programs to affect cell fate.Rapid changes in cellular gene expression are often brought about by regulation at the level of protein synthesis from existing mRNA transcripts. Such alterations are particularly important under conditions of cellular stress and apoptosis, and during certain stages of mitosis 1 . Cellular stresses such as viral infection or nutrient deprivation lead to an almost immediate shutdown of general translation accompanied by cleavage or covalent modification of one or more of the eukaryotic initiation factors (eIFs) 2-5 . However, this attenuation of translation is typically accompanied by a selective increase in the translation of specific regulatory proteins 6-9 whose sustained expression can affect cell fate 1,10 . How particular mRNAs are selectively translated during periods of global translation inhibition is not well understood.

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Ribosome inactivating proteins and apoptosis

Cited by 137 publications

References 51 publications

Cytological and Subcellular Response of Cells Exposed to the Type-1 RIP Curcin and its Hemocompatibility Analysis

Cytological and Subcellular Response of Cells Exposed to the Type-1 RIP Curcin and its Hemocompatibility Analysis

Ribosome Depurination Is Not Sufficient for Ricin-Mediated Cell Death in Saccharomyces cerevisiae

Direct ribosomal binding by a cellular inhibitor of translation

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