The protein pheromone Er-1 of the ciliate Euplotes raikovi stimulates human T-cell activity: Involvement of interleukin-2 system

Cervia, Davide; Catalani, Elisabetta; Belardinelli, Maria Cristina; Perrotta, Cristiana; Picchietti, Simona; Alimenti, Claudio; Casini, G.; Fausto, Anna Maria; Vallesi, Adriana

doi:10.1016/j.yexcr.2012.10.007

Cited by 15 publications

(20 citation statements)

References 57 publications

(83 reference statements)

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“…Using published protocols16353637383940, cell viability of P3X, PC12, AtT-20, 3T3, and B16-F10 cells was evaluated by MTT analysis. MTT absorbance was quantified spectrophotometrically using a Glomax Multi Detection System microplate reader (Promega, Milano, Italy).…”

Section: Methodsmentioning

confidence: 99%

Climacostol reduces tumour progression in a mouse model of melanoma via the p53-dependent intrinsic apoptotic programme

Perrotta

Buonanno

Zecchini

et al. 2016

Sci Rep

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Climacostol, a compound produced by the ciliated protozoan Climacostomum virens, displayed cytotoxic properties in vitro. This study demonstrates that it has anti-tumour potential. Climacostol caused a reduction of viability/proliferation of B16-F10 mouse melanoma cells, a rapidly occurring DNA damage, and induced the intrinsic apoptotic pathway characterised by the dissipation of the mitochondrial membrane potential, the translocation of Bax to the mitochondria, the release of Cytochrome c from the mitochondria, and the activation of Caspase 9-dependent cleavage of Caspase 3. The apoptotic mechanism of climacostol was found to rely on the up-regulation of p53 and its targets Noxa and Puma. In vivo analysis of B16-F10 allografts revealed a persistent inhibition of tumour growth rate when melanomas were treated with intra-tumoural injections of climacostol. In addition, it significantly improved the survival of transplanted mice, decreased tumour weight, induced a remarkable reduction of viable cells inside the tumour, activated apoptosis and up-regulated the p53 signalling network. Importantly, climacostol toxicity was more selective against tumour than non-tumour cells. The anti-tumour properties of climacostol and the molecular events associated with its action indicate that it is a powerful agent that may be considered for the design of pro-apoptotic drugs for melanoma therapy.

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Section: Methodsmentioning

confidence: 99%

Climacostol reduces tumour progression in a mouse model of melanoma via the p53-dependent intrinsic apoptotic programme

Perrotta

Buonanno

Zecchini

et al. 2016

Sci Rep

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“…As described in Section IX, in Euplotes raikovi a pheromone released into the medium can activate, via an autocrine pathway, a mitogenic cascade involving MAPK activity (Vallesi et al, ). Important signalling steps are activated when the Euplotes raikovi pheromone, Er‐1, is applied to human T‐cells (Cervia et al, ). These data suggest rather extensive effects on the promotion of mitotic activity also in Euplotes raikovi .…”

Section: Surface Receptors For Intracellular Signallingmentioning

confidence: 99%

Signalling in ciliates: long- and short-range signals and molecular determinants for cellular dynamics

Plattner

2015

Biol Rev

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In ciliates, unicellular representatives of the bikont branch of evolution, inter- and intracellular signalling pathways have been analysed mainly in Paramecium tetraurelia, Paramecium multimicronucleatum and Tetrahymena thermophila and in part also in Euplotes raikovi. Electrophysiology of ciliary activity in Paramecium spp. is a most successful example. Established signalling mechanisms include plasmalemmal ion channels, recently established intracellular Ca -release channels, as well as signalling by cyclic nucleotides and Ca . Ca -binding proteins (calmodulin, centrin) and Ca -activated enzymes (kinases, phosphatases) are involved. Many organelles are endowed with specific molecules cooperating in signalling for intracellular transport and targeted delivery. Among them are recently specified soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNAREs), monomeric GTPases, H -ATPase/pump, actin, etc. Little specification is available for some key signal transducers including mechanosensitive Ca -channels, exocyst complexes and Ca -sensor proteins for vesicle-vesicle/membrane interactions. The existence of heterotrimeric G-proteins and of G-protein-coupled receptors is still under considerable debate. Serine/threonine kinases dominate by far over tyrosine kinases (some predicted by phosphoproteomic analyses). Besides short-range signalling, long-range signalling also exists, e.g. as firmly installed microtubular transport rails within epigenetically determined patterns, thus facilitating targeted vesicle delivery. By envisaging widely different phenomena of signalling and subcellular dynamics, it will be shown (i) that important pathways of signalling and cellular dynamics are established already in ciliates, (ii) that some mechanisms diverge from higher eukaryotes and (iii) that considerable uncertainties still exist about some essential aspects of signalling.

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“…The three-helix molecular fold of the Euplotes pheromones finds relevant similarities in a variety of other helical and disulfide-rich signaling proteins, such as gastropod attractins, sea anemone peptide toxins, anaphylotoxins and others, produced by multicellular organisms (Cheek et al 2006). These similarities well account for the intriguing capability of someEuplotes pheromones to cross-react with very distantly related cell systems such as mammalian lymphocyte cell lines (Vallesi et al 1998;Cervia et al, 2013). Although these cross-reactions most likely reflect fortuitous cases of structural convergence, their occurrence implies the early evolution of cell-cell signaling mechanisms via water-borne pheromones, and stimulates further structural investigations on ciliate pheromones in view of possible applied purposes.…”

Section: Discussionmentioning

confidence: 95%

Revisiting fifty years of research on pheromone signaling in ciliates

Luporini

Pedrini

Alimenti

et al. 2016

European Journal of Protistology

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Among protists, pheromones have been identified in a great variety of algal species for their activity in driving gamete-gamete interactions for fertilization. Analogously in ciliates, pheromones have been identified for their activity in inducing the sexual phenomenon of conjugation. Although this identification was pioneered by Kimball more than fifty years ago, an effective isolation and chemical characterization of ciliate pheromones has remained confined to species of Blepharisma, Dileptus and Euplotes. In Euplotes species, in which the molecular structures have been determined, pheromones form species-specific families of structurally homologous helical, cysteine-rich, highly-stable proteins. Being structurally homologous, they can bind cells in competition with one another, raising interesting functional analogies with the families of growth factors and cytokines that regulate cell differentiation and development in higher organisms. In addition to inducing conjugation by binding cells in heterologous fashion, Euplotes pheromones act also as autocrine growth factors by binding to, and promoting the vegetative reproduction of the same cells from which they originate. This autocrine activity is most likely primary, providing a concrete example of how the original function of a molecule can be obscured during evolution by the acquisition of a new one.

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The protein pheromone Er-1 of the ciliate Euplotes raikovi stimulates human T-cell activity: Involvement of interleukin-2 system

Cited by 15 publications

References 57 publications

Climacostol reduces tumour progression in a mouse model of melanoma via the p53-dependent intrinsic apoptotic programme

Climacostol reduces tumour progression in a mouse model of melanoma via the p53-dependent intrinsic apoptotic programme

Signalling in ciliates: long- and short-range signals and molecular determinants for cellular dynamics

Revisiting fifty years of research on pheromone signaling in ciliates

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