Beyond UPR: cell-specific roles of ER stress sensor IRE1α in kidney ischemic injury and transplant rejection

Qiu, Longhui; Zheng, Xiaohui; Jaishankar, Dinesh; Green, Richard; Fang, Deyu; Nadig, Satish N.; Zhang, Zheng Jenny

doi:10.1016/j.kint.2023.06.016

Cited by 7 publications

(2 citation statements)

References 41 publications

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“…Upon GRP78 dissociation, IRE1 undergoes dimerization and autophosphorylation, activating its endoribonuclease activity ( Bhardwaj et al, 2020 ). The spliced form of X box-binding protein 1 (XBP1-S), produced after RNase cleavage, functions as a transcription factor that translocates to the nucleus ( Qiu et al, 2023 ). This initiates the expression of genes coordinating protein transcription and translation, lipid synthesis, ERAD, and proteins maintaining ER homeostasis during stress.…”

Section: Er Stress and Upr Activation: From Molecular Pathways To Cel...mentioning

confidence: 99%

Endoplasmic reticulum stress and quality control in relation to cisplatin resistance in tumor cells

Mu,

Zhi,

Zhou

et al. 2024

Front. Pharmacol.

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The endoplasmic reticulum (ER) is a crucial organelle that orchestrates key cellular functions like protein folding and lipid biosynthesis. However, it is highly sensitive to disturbances that lead to ER stress. In response, the unfolded protein response (UPR) activates to restore ER homeostasis, primarily through three sensors: IRE1, ATF6, and PERK. ERAD and autophagy are crucial in mitigating ER stress, yet their dysregulation can lead to the accumulation of misfolded proteins. Cisplatin, a commonly used chemotherapy drug, induces ER stress in tumor cells, activating complex signaling pathways. Resistance to cisplatin stems from reduced drug accumulation, activation of DNA repair, and anti-apoptotic mechanisms. Notably, cisplatin-induced ER stress can dualistically affect tumor cells, promoting either survival or apoptosis, depending on the context. ERAD is crucial for degrading misfolded proteins, whereas autophagy can protect cells from apoptosis or enhance ER stress-induced apoptosis. The complex interaction between ER stress, cisplatin resistance, ERAD, and autophagy opens new avenues for cancer treatment. Understanding these processes could lead to innovative strategies that overcome chemoresistance, potentially improving outcomes of cisplatin-based cancer treatments. This comprehensive review provides a multifaceted perspective on the complex mechanisms of ER stress, cisplatin resistance, and their implications in cancer therapy.

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Section: Er Stress and Upr Activation: From Molecular Pathways To Cel...mentioning

confidence: 99%

Endoplasmic reticulum stress and quality control in relation to cisplatin resistance in tumor cells

Mu,

Zhi,

Zhou

et al. 2024

Front. Pharmacol.

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“…ER is central to protein synthesis, transport, and posttranslational modification, in addition to serving as a reservoir for intracellular calcium [ 6 ]. ER stress, triggered by the accumulation of unfolded and misfolded protein riggers glucose-related protein 78 (GRP78, also known as binding immunoglobulin protein, BiP), activates the unfolded protein response (UPR) through sensors like protein kinase R‐like ER kinase (PERK), inositol requiring enzyme 1‐α (IRE1‐α), and activating transcription factor 6 (ATF6) [ 7 , 8 ]. This leads to the upregulation of CCAAT/enhancer-binding protein homologous protein (CHOP), a major facilitator of programmed cell death, thereby contributing to kidney disease progression, including AKI [ 4 , 9 ].…”

Section: Introductionmentioning

confidence: 99%

DDRGK1-mediated ER-phagy attenuates acute kidney injury through ER-stress and apoptosis

Jin,

Yang,

Zhu

et al. 2024

Cell Death Dis

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Acute kidney injury (AKI) constitutes a prevalent clinical syndrome characterized by elevated morbidity and mortality rates, emerging as a significant public health issue. This study investigates the interplay between endoplasmic reticulum (ER) stress, unfolded protein response (UPR), and ER-associated degradation (ER-phagy) in the pathogenesis of AKI. We employed four distinct murine models of AKI—induced by contrast media, ischemia–reperfusion injury, cisplatin, and folic acid—to elucidate the relationship between ER-phagy, ER stress, and apoptosis. Our findings reveal a marked decrease in ER-phagy coinciding with an accumulation of damaged ER, elevated ER stress, and increased apoptosis across all AKI models. Importantly, overexpression of DDRGK1 in HK-2 cells enhanced ER-phagy levels, ameliorating contrast-induced ER stress and apoptosis. These findings unveil a novel protective mechanism in AKI, wherein DDRGK1–UFL1-mediated ER-phagy mitigates ER stress and apoptosis in renal tubular epithelial cells. Our results thereby contribute to understanding the molecular underpinnings of AKI and offer potential therapeutic targets for its treatment.

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The emerging roles of UFMylation in the modulation of immune responses

Liang,

Ning,

Wang

et al. 2024

Clinical & Translational Med

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Post‐translational modification is a rite of passage for cellular functional proteins and ultimately regulate almost all aspects of life. Ubiquitin‐fold modifier 1 (UFM1) system represents a newly identified ubiquitin‐like modification system with indispensable biological functions, and the underlying biological mechanisms remain largely undiscovered. The field has recently experienced a rapid growth of research revealing that UFMylation directly or indirectly regulates multiple immune processes. Here, we summarised important advances that how UFMylation system responds to intrinsic and extrinsic stresses under certain physiological or pathological conditions and safeguards immune homeostasis, providing novel perspectives into the regulatory framework and functions of UFMylation system, and its therapeutic applications in human diseases.

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Beyond UPR: cell-specific roles of ER stress sensor IRE1α in kidney ischemic injury and transplant rejection

Cited by 7 publications

References 41 publications

Endoplasmic reticulum stress and quality control in relation to cisplatin resistance in tumor cells

Endoplasmic reticulum stress and quality control in relation to cisplatin resistance in tumor cells

DDRGK1-mediated ER-phagy attenuates acute kidney injury through ER-stress and apoptosis

The emerging roles of UFMylation in the modulation of immune responses

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