Phospholipase Cγ in Toll-like receptor-mediated inflammation and innate immunity

Bae, Yoe‐Sik; Lee, Ha Young; Jung, Young Su; Lee, Mingyu; Suh, Pann‐Ghill

doi:10.1016/j.jbior.2016.09.006

Cited by 27 publications

(26 citation statements)

References 61 publications

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“…Indeed, the PI cycle usually includes PLC (13, 14), a class of enzymes able to hydrolyze phosphatidylinositol 4,5‐biphosphate to produce inositol 1,4,5‐trisphosphate and diacylglycerol, whose nuclear localization is involved in the activation of PKCs (15). Therefore, the PI cycle has an essential role in the regulation of cell proliferation and differentiation (16–18) but is also implicated in immunomodulation processes (19).…”

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confidence: 99%

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Nuclear translocation of PKC‐ α is associated with cell cycle arrest and erythroid differentiation in myelodysplastic syndromes (MDSs)

et al. 2018

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PI-PLCβ1 is involved in cell proliferation, differentiation, and myelodysplastic syndrome (MDS) pathogenesis. Moreover, the increased activity of PI-PLCβ1 reduces the expression of PKC-α, which, in turn, delays the cell proliferation and is linked to erythropoiesis. Lenalidomide is currently used in low-risk patients with MDS and del(5q), where it can suppress the del(5q) clone and restore normal erythropoiesis. In this study, we analyzed the effect of lenalidomide on 16 patients with low-risk del(5q) MDS, as well as del(5q) and non-del(5q) hematopoietic cell lines, mainly focusing on erythropoiesis, cell cycle, and PI-PLCβ1/PKC-α signaling. Overall, 11 patients were evaluated clinically, and 10 (90%) had favorable responses; the remaining case had a stable disease. At a molecular level, both responder patients and del(5q) cells showed a specific induction of erythropoiesis, with a reduced γ/β-globin ratio, an increase in glycophorin A, and a nuclear translocation of PKC-α. Moreover, lenalidomide could induce a selective G/G arrest of the cell cycle in del(5q) cells, slowing down the rate proliferation in those cells. Altogether, our results could not only better explain the role of PI-PLCβ1/PKC-α signaling in erythropoiesis but also lead to a better comprehension of the lenalidomide effect on del(5q) MDS and pave the way to innovative, targeted therapies.-Poli, A., Ratti, S., Finelli, C., Mongiorgi, S., Clissa, C., Lonetti, A., Cappellini, A., Catozzi, A., Barraco, M., Suh, P.-G., Manzoli, L., McCubrey, J. A., Cocco, L., Follo, M. Y. Nuclear translocation of PKC-α is associated with cell cycle arrest and erythroid differentiation in myelodysplastic syndromes (MDSs).

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confidence: 99%

“…whose nuclear localization is involved in the activation of PKCs (15). Therefore, the PI cycle has an essential role in the regulation of cell proliferation and differentiation (16)(17)(18) but is also implicated in immunomodulation processes (19).…”

mentioning

confidence: 99%

Nuclear translocation of PKC‐ α is associated with cell cycle arrest and erythroid differentiation in myelodysplastic syndromes (MDSs)

et al. 2018

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“…Src) and catalyzes the formation of the second messenger IP3 and DAG. Recently PLCG1 was also found to impact progression of HCC [42], the HCV replication cycle [43], as well as receptor-mediated inflammation and innate immunity Host factor prioritization for pan-viral genetic perturbation screens [44]. EP300 is an acetyltransferase and acts as a transcriptional co-activator and has not been studied in detail so far.…”

Section: Biological Resultsmentioning

confidence: 99%

Host factor prioritization for pan-viral genetic perturbation screens using random intercept models and network propagation

et al. 2020

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Genetic perturbation screens using RNA interference (RNAi) have been conducted successfully to identify host factors that are essential for the life cycle of bacteria or viruses. So far, most published studies identified host factors primarily for single pathogens. Furthermore, often only a small subset of genes, e.g., genes encoding kinases, have been targeted. Identification of host factors on a pan-pathogen level, i.e., genes that are crucial for the replication of a diverse group of pathogens has received relatively little attention, despite the fact that such common host factors would be highly relevant, for instance, for devising broadspectrum anti-pathogenic drugs. Here, we present a novel two-stage procedure for the identification of host factors involved in the replication of different viruses using a combination of random effects models and Markov random walks on a functional interaction network. We first infer candidate genes by jointly analyzing multiple perturbations screens while at the same time adjusting for high variance inherent in these screens. Subsequently the inferred estimates are spread across a network of functional interactions thereby allowing for the analysis of missing genes in the biological studies, smoothing the effect sizes of previously found host factors, and considering a priori pathway information defined over edges of the network. We applied the procedure to RNAi screening data of four different positive-sense single-stranded RNA viruses, Hepatitis C virus, Chikungunya virus, Dengue virus and Severe acute respiratory syndrome coronavirus, and detected novel host factors, including UBC, PLCG1, and DYRK1B, which are predicted to significantly impact the replication cycles of these viruses. We validated the detected host factors experimentally using pharmacological inhibition and an additional siRNA screen and found that some of the predicted host factors indeed influence the replication of these pathogens.

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“…The presence of autoinflammation in patients with evidence of autoimmunity and/or immunodeficiency highlights that the divide between the innate and adaptive immune system is not strict. 129 The initial description of PLAID investigated three families with dominantly inherited cold-induced urticaria, antibody deficiency and autoimmunity. 127,128 PLCγ2 is a phospholipase involved in immune signalling pathways and intracellular calcium release.…”

Section: Immunological Overlapmentioning

confidence: 99%

“…127,128 PLCγ2 is a phospholipase involved in immune signalling pathways and intracellular calcium release. 129 The initial description of PLAID investigated three families with dominantly inherited cold-induced urticaria, antibody deficiency and autoimmunity. 128 APLAID, on the other hand, was diagnosed in individuals with prominent inflammatory manifestations involving the skin, gut, bronchioles and uvea.…”

Section: Immunological Overlapmentioning

confidence: 99%

Monogenic autoinflammatory disorders: beyond the periodic fever

Moghaddas

2020

Internal Medicine Journal

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The past two decades have seen an exponential increase in the number of monogenic autoinflammatory disorders described, coinciding with improved genetic sequencing techniques. This group of disorders has evolved to be heterogeneous and certainly more complex than the original four ‘periodic fever syndromes’ caused by innate immune over‐activation. This review aims to provide an update on the classic periodic fever syndromes as well as introducing the broadening spectrum of clinical features seen in more recently described conditions.

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Phospholipase Cγ in Toll-like receptor-mediated inflammation and innate immunity

Cited by 27 publications

References 61 publications

Nuclear translocation of PKC‐ α is associated with cell cycle arrest and erythroid differentiation in myelodysplastic syndromes (MDSs)

Nuclear translocation of PKC‐ α is associated with cell cycle arrest and erythroid differentiation in myelodysplastic syndromes (MDSs)

Host factor prioritization for pan-viral genetic perturbation screens using random intercept models and network propagation

Monogenic autoinflammatory disorders: beyond the periodic fever

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