Mammalian apoptotic signalling pathways: multiple targets of protozoan parasites to activate or deactivate host cell death

Graumann, Kristin; Hippe, Diana; Groß, Uwe; Lüder, Carsten G. K.

doi:10.1016/j.micinf.2009.08.011

Cited by 15 publications

(10 citation statements)

References 50 publications

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“…HSP are also closely linked to host cell apoptosis, since certain members exhibit anti-apoptotic effects via both the receptor-mediated pathway and the inner, mitochondrial pathway [3, 4]. It is well known that intracellular stages of other apicomplexan parasites modulate host cell apoptosis to guarantee successful intracellular development (for review see [12]). Lang et al [18] have recently shown that E. bovis- infected cells are defended from apoptosis by enhanced expression of the anti-apoptotic molecules c-FLIP and c-IAP1.…”

Section: Discussionmentioning

confidence: 99%

Microarray-based transcriptional profiling ofEimeria bovis-infected bovine endothelial host cells

et al. 2010

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Within its life cycle Eimeria bovis undergoes a long lasting intracellular development into large macromeronts in endothelial cells. Since little is known about the molecular basis of E. bovis-triggered host cell regulation we applied a microarray-based approach to define transcript variation in bovine endothelial cells early after sporozoite invasion (4 h post inoculation (p.i.)), during trophozoite establishment (4 days p.i.), during early parasite proliferation (8 days p.i.) and towards macromeront maturation (14 days p.i.). E. bovis infection led to significant changes in the abundance of many host cell gene transcripts. As infection progressed, the number of regulated genes increased such that 12, 45, 175 and 1184 sequences were modulated at 4 h, 4, 8 and 14 days p.i., respectively. These genes significantly interfered with several host cell functions, networks and canonical pathways, especially those involved in cellular development, cell cycle, cell death, immune response and metabolism. The correlation between stage of infection and the number of regulated genes involved in different aspects of metabolism suggest parasite-derived exploitation of host cell nutrients. The modulation of genes involved in cell cycle arrest and host cell apoptosis corresponds to morphological in vitro findings and underline the importance of these aspects for parasite survival. Nevertheless, the increasing numbers of modulated transcripts associated with immune responses also demonstrate the defensive capacity of the endothelial host cell. Overall, this work reveals a panel of novel candidate genes involved in E. bovis-triggered host cell modulation, providing a valuable tool for future work on this topic.

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Section: Discussionmentioning

confidence: 99%

Microarray-based transcriptional profiling ofEimeria bovis-infected bovine endothelial host cells

et al. 2010

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“…Ermanno Candolfi and Alexander W. Pfaff To achieve intracellular persistence, T. gondii modulates and hijacks host cell pathways involved in various processes such as inflammation, apoptosis, metabolism, and cell growth [4]. This prevents infected cells from apoptosis and subverts the host's immune system [5,6]. The parasite manipulates the host cell signaling pathways by secreting kinases and phosphatases, of which some infiltrate the host cell nucleus and modulate gene expression activity.…”

Section: Cellular and Molecular Life Sciencesmentioning

confidence: 99%

Toxoplasma gondii ROP16 kinase silences the cyclin B1 gene promoter by hijacking host cell UHRF1-dependent epigenetic pathways

Sabou

Doderer-Lang

Leyer

et al. 2019

Cell. Mol. Life Sci.

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Toxoplasmosis, caused by the apicomplexan parasite Toxoplasma gondii, is one of the most common infections in the world due to the lifelong persistence of this parasite in a latent stage. This parasite hijacks host signaling pathways through epigenetic mechanisms which converge on key nuclear proteins. Here, we report a new parasite persistence strategy involving T. gondii rhoptry protein ROP16 secreted early during invasion, which targets the transcription factor UHRF1 (ubiquitinlike containing PHD and RING fingers domain 1), and leads to host cell cycle arrest. This is mediated by DNMT activity and chromatin remodeling at the cyclin B1 gene promoter through recruitment of phosphorylated UHRF1 associated with a repressive multienzymatic protein complex. This leads to deacetylation and methylation of histone H3 surrounding the cyclin B1 promoter to epigenetically silence its transcriptional activity. Moreover, T. gondii infection causes DNA hypermethylation in its host cell, by upregulation of DNMTs. ROP16 is already known to activate and phosphorylate protective immunity transcription factors such as STAT 3/6/5 and modulate host signaling pathways in a strain-dependent manner. Like in the case of STAT6, the strain-dependent effects of ROP16 on UHRF1 are dependent on a single amino-acid polymorphism in ROP16. This study demonstrates that Toxoplasma hijacks a new epigenetic initiator, UHRF1, through an early event initiated by the ROP16 parasite kinase.Keywords Toxoplasma gondii · UHFR1 · ROP16 · Cyclin B1 · DNMT · Epigenetic regulation Publisher's Note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

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“…Previous studies have demonstrated that ligand binding induces receptor clustering and recruitment of the adaptor protein FADD and the initiator caspases-8 and -10 as procaspases, forming a death-inducing signaling complex (DISC) ( 12 ). This event triggers the activation of the apical caspases including caspase-8 and -10, driving their autocatalytic processing and release into the cytoplasm, where they activate the effector caspases -3, -6 and -7 ( 18 , 19 ) ( Fig. 1 ).…”

Section: Introduction: Overview Of Cell Death and Its Intracellulamentioning

confidence: 99%

Molecular mechanisms of cell death in intervertebral disc degeneration (Review)

Zhang

Zhao

Shen

et al. 2016

International Journal of Molecular Medicine

194

176

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Intervertebral discs (IVDs) are complex structures that consist of three parts, namely, nucleus pulposus, annulus fibrosus and cartilage endplates. With aging, IVDs gradually degenerate as a consequence of many factors, such as microenvironment changes and cell death. Human clinical trial and animal model studies have documented that cell death, particularly apoptosis and autophagy, significantly contribute to IVD degeneration. The mechanisms underlying this phenomenon include the activation of apoptotic pathways and the regulation of autophagy in response to nutrient deprivation and multiple stresses. In this review, we briefly summarize recent progress in understanding the function and regulation of apoptosis and autophagy signaling pathways. In particular, we focus on studies that reveal the functional mechanisms of these pathways in IVD degeneration.

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Mammalian apoptotic signalling pathways: multiple targets of protozoan parasites to activate or deactivate host cell death

Cited by 15 publications

References 50 publications

Microarray-based transcriptional profiling ofEimeria bovis-infected bovine endothelial host cells

Microarray-based transcriptional profiling ofEimeria bovis-infected bovine endothelial host cells

Toxoplasma gondii ROP16 kinase silences the cyclin B1 gene promoter by hijacking host cell UHRF1-dependent epigenetic pathways

Molecular mechanisms of cell death in intervertebral disc degeneration (Review)

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