ArticlePloS one2013
Interleukin-1 receptor-associated kinase-2 (IRAK2) is a critical mediator of endoplasmic reticulum (ER) stress signaling.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 26 citations in OpenAlex.
- IRAK2, an Immune and Radiation-Response Gene, Correlates with Advanced Disease Features but Predicts Higher Post-Irradiation Local Control in Non-Metastatic and Resected Oral Cancer Patients.International journal of molecular sciences · 2023Article
- IRAK2 Downregulation in Triple-Negative Breast Cancer Cells Decreases Cellular Growth In Vitro and Delays Tumour Progression in Murine Models.International journal of molecular sciences · 2023Article
- Potential Protection Effect of ER Homeostasis of NInternational journal of molecular sciences · 2021Article
- IRAK2, an IL1R/TLR Immune Mediator, Enhances RadiosensitivityFrontiers in oncology · 2021Article
- Deep insights into the response of human cervical carcinoma cells to a new cyano enone-bearing triterpenoid soloxolone methyl: a transcriptome analysis.Oncotarget · 2019Article
- Kaempferol mitigates Endoplasmic Reticulum Stress Induced Cell Death by targeting caspase 3/7.Scientific reports · 2018Article
- Shear stress induces human aortic endothelial cell apoptosis via interleukin‑1 receptor‑associated kinase 2‑induced endoplasmic reticulum stress.Molecular medicine reports · 2017Article
- Identification of Doxorubicin as an Inhibitor of the IRE1α-XBP1 Axis of the Unfolded Protein Response.Scientific reports · 2016Article
- Exploring the Conserved Role of MANF in the Unfolded Protein Response in Drosophila melanogaster.PloS one · 2016Article
- Nucleotide-binding mechanisms in pseudokinases.Bioscience reports · 2015Review
- Circulating interleukin-1β promotes endoplasmic reticulum stress-induced myocytes apoptosis in diabetic cardiomyopathy via interleukin-1 receptor-associated kinase-2.Cardiovascular diabetology · 2015Article
- Cell type-specific transcriptomics of hypothalamic energy-sensing neuron responses to weight-loss.eLife · 2015Article
- RIPK1 promotes death receptor-independent caspase-8-mediated apoptosis under unresolved ER stress conditions.Cell death & disease · 2014Article
- Interleukin-1 receptor-associated kinase-2 genetic variant rs708035 increases NF-κB activity through promoting TRAF6 ubiquitination.The Journal of biological chemistry · 2014Article
- A molecular web: endoplasmic reticulum stress, inflammation, and oxidative stress.Frontiers in cellular neuroscience · 2014Review
- Effects of different tissue microenvironments on gene expression in breast cancer cells.PloS one · 2014Article
Corrections and comments
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Authors and funding
14 authors at 3 institutions in 1 country.
Funding
Abstract
Endoplasmic reticulum (ER) stress occurs when unfolded proteins accumulate in the lumen of the organelle, triggering signal transduction events that contribute either to cellular adaptation and recovery or alternatively to cellular dysfunction and death. ER stress has been implicated in numerous diseases. To identify novel modulators of ER stress, we undertook a siRNA library screen of the kinome, revealing Interleukin-1 Receptor-Associated Kinase-2 (IRAK2) as a contributor to unfolded protein response (UPR) signaling and ER stress-induced cell death. Knocking down expression of IRAK2 (but not IRAK1) in cultured mammalian cells suppresses ER stress-induced expression of the pro-apoptotic transcription factor CHOP and activation of stress kinases. Similarly, RNAi-mediated silencing of the IRAK family member Tube (but not Pelle) suppresses activation of stress kinase signaling induced by ER stress in Drosophila cells. The action of IRAK2 maps to the IRE1 pathway, rather than the PERK or ATF6 components of the UPR. Interestingly, ER stress also induces IRAK2 gene expression in an IRE1/XBP1-dependent manner, suggesting a mutually supporting amplification loop involving IRAK2 and IRE1. In vivo, ER stress induces Irak2 expression in mice. Moreover, Irak2 gene knockout mice display defects in ER stress-induced CHOP expression and IRE1 pathway signaling. These findings demonstrate an unexpected linkage of the innate immunity machinery to UPR signaling, revealing IRAK2 as a novel amplifier of the IRE1 pathway.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.