ArticleCell death & disease2017
HRD1 prevents apoptosis in renal tubular epithelial cells by mediating eIF2α ubiquitylation and degradation.
Article in Cell death & disease, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 51 citations in OpenAlex.
- Ubiquitin and ubiquitin-like modifications in the endoplasmic reticulum stress response.The FEBS journal · 2026Review
- Post‑translational modifications in diabetic kidney disease (Review).International journal of molecular medicine · 2026Review
- The UFM1 Conjugation System: A Master Regulator of Cellular Stress Surveillance in Human Disease.Biology · 2026Review
- Unfolded protein response in bronchopulmonary dysplasia: mechanisms, pathways, and therapeutic implications.Frontiers in cell and developmental biology · 2026Review
- Targeting programmed cell death in diabetic kidney disease: from molecular mechanisms to pharmacotherapy.Molecular medicine (Cambridge, Mass.) · 2024Review
- Article
- Casting Light on the Janus-Faced HMG-CoA Reductase Degradation Protein 1: A Comprehensive Review of Its Dualistic Impact on Apoptosis in Various Diseases.Molecular neurobiology · 2024Review
- Renal tubular epithelial cell quality control mechanisms as therapeutic targets in renal fibrosis.Journal of pharmaceutical analysis · 2024Review
- HIF-1α participates in the regulation of S100A16-HRD1-GSK3β/CK1α pathway in renal hypoxia injury.Cell death & disease · 2024Article
- The ubiquitin codes in cellular stress responses.Protein & cell · 2024Review
- Endoplasmic reticulum stress in diabetic kidney disease: adaptation and apoptosis after three UPR pathways.Apoptosis : an international journal on programmed cell death · 2023Review
- SYVN1 Promotes STAT3 Protein Ubiquitination and Exerts Antiangiogenesis Effects in Retinopathy of Prematurity Development.Investigative ophthalmology & visual science · 2023Article
- Molecular Characterization of Esophageal Squamous Cell Carcinoma Using Quantitative Proteomics.Cancers · 2023Article
- Role of renal tubular programed cell death in diabetic kidney disease.Diabetes/metabolism research and reviews · 2023Review
- Fenofibrate Attenuates Renal Tubular Cell Apoptosis by Up-Regulating MCAD in Diabetic Kidney Disease.Drug design, development and therapy · 2023Article
- The role of Chinese herbal medicine in the treatment of diabetic nephropathy by regulating endoplasmic reticulum stress.Frontiers in pharmacology · 2023Review
- Endoplasmic Reticulum Stress in Chronic Obstructive Pulmonary Disease: Mechanisms and Future Perspectives.Biomolecules · 2022Review
- TMBIM6 promotes diabetic tubular epithelial cell survival and albumin endocytosis by inhibiting the endoplasmic reticulum stress sensor, IRE1α.Molecular biology reports · 2022Article
- Ginsenoside Rb1 alleviates colitis in mice via activation of endoplasmic reticulum-resident E3 ubiquitin ligase Hrd1 signaling pathway.Acta pharmacologica Sinica · 2021Article
- Zonisamide, an antiepileptic drug, alleviates diabetic cardiomyopathy by inhibiting endoplasmic reticulum stress.Acta pharmacologica Sinica · 2021Article
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Apoptosis of renal tubular epithelial cells is a key feature of the pathogenicity associated with tubulointerstitial fibrosis and other kidney diseases. One factor that regulates important cellular processes like apoptosis and cell proliferation is HRD1, an E3 ubiquitin ligase that acts by promoting ubiquitylation and degradation of its target protein. However, the detailed mechanisms by which HRD1 acts as a regulator of apoptosis in renal tubular epithelial cells have not been established. In our previous liquid chromatography-tandem mass spectrometry (LC-MS/MS) study (Mol Endocrinol. 2016;30:600-613), we demonstrated that one substrate of HRD1 was eIF2α, a critical protein in the PERK-eIF2α-ATF4-CHOP signaling pathway of endoplasmic reticulum (ER) stress. Here, we show that eIF2α expression was increased and HRD1 expression decreased when apoptosis was induced in HKC-8 cells by palmitic acid (PA) or high glucose (HG). HRD1 expression was also lower in kidney tissues from mice with diabetic nephropathy (DN) than in control mice. Forced expression of HRD1 also inhibited apoptosis in HKC-8 cells, while HRD1 overexpression decreased the expression of phosphorylated eIF2α and eIF2α. Further analysis indicated that HRD1 interacted with eIF2α and promoted its ubiquitylation and degradation by the proteasome. Moreover, the HRD1 protection of PA-treated HKC-8 cells was blunted by transfection with Myc-eIF2α. Thus, eIF2α ubiquitylation by HRD1 protects tubular epithelial cells from apoptosis caused by HG and PA, indicating a novel upstream target for therapeutic prevention of renal tubulointerstitial injury.
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