The Emerging Roles of NDR1/2 in Infection and Inflammation

Ye, Xiaolan; Ong, Naomi; An, Huazhang; Zheng, Yuejuan

doi:10.3389/fimmu.2020.00534

Cited by 21 publications

(18 citation statements)

References 68 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The Hippo pathway key effectors, YAP and/or TAZ, were reported to be mediators or regulators of many inflammatory processes 72 – 74 . Furthermore, the role of other components of the Hippo pathway, including NDR1/2 75 and MST1 76 in inflammation has been emerging within recent years.…”

Section: The Hippo Pathwaymentioning

confidence: 99%

“…The Hippo pathway key effectors, YAP and/or TAZ, were reported to be mediators or regulators of many inflammatory processes [72][73][74] . Furthermore, the role of other components of the Hippo pathway, including NDR1/2 75 and MST1 76 in inflammation has been emerging within recent years. A prototypical proinflammatory cytokine, IL-6 77 , was found to potently activate YAP and Notch by binding its co-receptor gp130 9 .…”

Section: Hippo and Pathways Involved In Inflammationmentioning

confidence: 99%

See 1 more Smart Citation

The role of the Hippo pathway in the pathogenesis of inflammatory bowel disease

et al. 2021

View full text Add to dashboard Cite

Inflammatory bowel disease (IBD) is a chronic and recurrent inflammatory disorder that primarily comprises Crohn’s disease (CD) and ulcerative colitis (UC). Owing to its increasing prevalence in Eastern countries and the intractable challenges faced during IBD treatment, extensive research on IBD has been carried out over the last few years. Although the precise aetiology of IBD is undefined, the currently accepted hypothesis for IBD pathogenesis considers it to be a combination of environment, genetic predisposition, gut microbiota, and abnormal immunity. A recently emerged signalling pathway, the Hippo pathway, acts as a key regulator of cell growth, tissue homoeostasis, organ size, and has been implicated in several human cancers. In the past few years, studies have revealed the importance of the Hippo pathway in gastrointestinal tract physiology and gastrointestinal diseases, such as colorectal cancer and IBD. However, the role of the Hippo pathway and its exact impact in IBD remains to be elucidated. This review summarises the latest scientific literature on the involvement of this pathway in IBD from the following perspectives that account for the IBD pathogenesis: intestinal epithelial cell regeneration, immune regulation, gut microbiota, and angiogenesis. A comprehensive understanding of the specific role of the Hippo pathway in IBD will provide novel insights into future research directions and clinical implications of the Hippo pathway.

show abstract

Section: The Hippo Pathwaymentioning

confidence: 99%

Section: Hippo and Pathways Involved In Inflammationmentioning

confidence: 99%

The role of the Hippo pathway in the pathogenesis of inflammatory bowel disease

et al. 2021

View full text Add to dashboard Cite

show abstract

“…The salient observation in this regard is the proteolytic cleavage of host PKs involved in innate immunity by HIV-1 PR. Nuclear Dbf2-related (NDR) kinases, NDR1 and NDR2 are essential PKs instrumental in regulating PRR and cytokines in innate immunity ( Ye et al, 2020 ) and HIV-PR has been shown to cleave both NDR1 and NDR2 ( Devroe et al, 2005 ). Similarly, receptor interacting protein kinases (RIPK) RIPK1 and RIPK3 are involved in eliminating virus infected cells through necroptosis and have also been shown to mediate type 1 IFN signaling for this purpose ( Rajput et al, 2011 ).…”

Section: Discussionmentioning

confidence: 99%

Cleavage of TANK-Binding Kinase 1 by HIV-1 Protease Triggers Viral Innate Immune Evasion

Jeremiah¹,

Miyakawa²,

Matsunaga³

et al. 2021

Front. Microbiol.

View full text Add to dashboard Cite

Type-I interferons (IFN-I) are the innate immune system’s principal defense against viral infections. Human immunodeficiency virus-1 (HIV-1) has evolved several ways to suppress or evade the host’s innate immunity in order to survive and replicate to sustain infection. Suppression of IFN-I is one among the multiple escape strategies used by HIV-1 to prevent its clearance. HIV-1 protease which helps in viral maturation has also been observed to cleave host cellular protein kinases. In this study we performed a comprehensive screening of a human kinase library using AlphaScreen assay and identified that TANK binding kinase-1 (TBK1) was cleaved by HIV-1 protease (PR). We demonstrate that PR cleaved TBK1 fails to phosphorylate IFN regulatory factor 3 (IRF3), thereby reducing the IFN-I promoter activity and further reveal that the PR mediated suppression of IFN-I could be counteracted by protease inhibitors (PI) in vitro. We have also revealed that mutations of HIV-1 PR that confer drug resistance to PIs reduce the enzyme’s ability to cleave TBK1. The findings of this study unearth a direct link between HIV-1 PR activity and evasion of innate immunity by the virus, the possible physiological relevance of which warrants to be determined.

show abstract

“…Dbf2p-related kinase 1 (NDR1) in the biomembrane-localized protein kinase belongs to the family of NDR-LATS protein kinases. It can positively regulate centrosome replication in a non-dependent manner, and participates in cell apoptosis, cycle regulation, and biological processes, such as autophagy [ 9 ]. Studies have confirmed that, when pathogenic microorganisms invade, inducing the expression of NDR1 can enhance the body’s resistance to pathogenic microorganism infection [ 10 ].…”

Section: Introductionmentioning

confidence: 99%

Molecular Mechanism of Biofilm Locator Protein Kinase Dbf2p-related kinase 1 in Regulating Innate Immune Response to Interleukin 17-induced Viral Pneumonia

Wang

Shu

et al. 2021

Bioengineered

View full text Add to dashboard Cite

It focused on the antiviral immune regulation of biofilm-localized protein kinase Dbf2p-related kinase 1 (NDR1) in viral pneumonia. Mouse alveolar monocyte RAW264.7 was used as blank control, and viral pneumonia cell model was prepared by infecting cells with respiratory syncytial virus (RSV). NDR1 overexpression vector and siRNA interference sequences were synthesized, and overexpression/silence NDR1 cell model was fabricated. About 50 ng/mL interleukin 17 (IL-17) was given to stimulate. Enzyme-linked immunosorbent assay (ELISA), quantitative reverse transcription PCR (RT-qRCR), and Western blot were performed to detect cytokines and chemokines, mRNA of inflammatory factors, and signal molecule protein expression. Notably, RSV infection increased RSV-F mRNA in RAW264.7 cells and reduced NDR1 mRNA and protein. Secretion levels of IL-6, interferon β (IFN-β), chemokine (C-X-C motif) ligand 2 (CXCL2), and chemokine (C-C motif) ligand 2 (CCL20) increased in the model group versus blank control ( P < 0.05). IL-6, IFN-β, tumor necrosis factor α (TNF-α), and toll-like receptor 3 (TLR3) mRNA were up-regulated ( P < 0.05). Extracellular signal-regulated kinase (ERK1/2), p38 protein phosphorylation, human recombinant 1 (TBK1), and nuclear factor kappa-B (NF-κB) protein levels increased ( P < 0.05). After overexpression of NDR1, the secretion levels of cytokines and chemokines, inflammatory factors mRNA, and signal molecule protein increased significantly. After NDR1 was silenced, cytokines and chemokines, inflammatory factors mRNA, and signal molecule protein were not significantly different versus blank control group ( P > 0.05). In short, NDR1 regulated innate immune response to viral pneumonia induced by IL-17, which can be used as a new target for the treatment of IL-17-induced inflammatory response and autoimmune diseases.

show abstract

The Emerging Roles of NDR1/2 in Infection and Inflammation

Cited by 21 publications

References 68 publications

The role of the Hippo pathway in the pathogenesis of inflammatory bowel disease

The role of the Hippo pathway in the pathogenesis of inflammatory bowel disease

Cleavage of TANK-Binding Kinase 1 by HIV-1 Protease Triggers Viral Innate Immune Evasion

Molecular Mechanism of Biofilm Locator Protein Kinase Dbf2p-related kinase 1 in Regulating Innate Immune Response to Interleukin 17-induced Viral Pneumonia

Contact Info

Product

Resources

About