ArticleThe Journal of biological chemistry2022
ERK/RSK-mediated phosphorylation of Y-box binding protein-1 aggravates diabetic cardiomyopathy by suppressing its interaction with deubiquitinase OTUB1.
Article in The Journal of biological chemistry, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 20 citations in OpenAlex.
- Crosstalk between ubiquitination and other post-translational modifications in cardiovascular diseases.iScience · 2026Review
- Phosphorylation of YBX1 in the Kidneys is Altered in Legumain Knockout-Mice.Journal of proteome research · 2026Article
- Targeting Integrin β3 in Endothelial Cells Attenuates Cardiac Fibrosis Through the Calcium-Calmodulin-Dependent Protein Kinase IIα- cAMP-Responsive Element Binding Protein 1 Signaling Axis in Pressure Overload-Induced Heart Failure.Journal of the American Heart Association · 2026Article
- Discovery of a Novel Small-Molecule Modulator for Full-length YB-1 Protein via Integrated Computational and in vitro Biophysical Approaches.Applied biochemistry and biotechnology · 2026Article
- OTU deubiquitinases as immune-circuit editors: from human immunopathology to therapeutic prioritization.Frontiers in immunology · 2026Review
- Cardiomyocyte-derived YOD1 promotes pathological cardiac hypertrophy by deubiquitinating and stabilizing STAT3.Science advances · 2025Article
- RSK1 and RSK2 as therapeutic targets: an up-to-date snapshot of emerging data.Expert opinion on therapeutic targets · 2024Review
- OTUB1 regulation of ferroptosis and the protective role of ferrostatin-1 in lupus nephritis.Cell death & disease · 2024Article
- Deubiquitinase USP25 Alleviates Obesity-Induced Cardiac Remodeling and Dysfunction by Downregulating TAK1 and Reducing TAK1-Mediated Inflammation.JACC. Basic to translational science · 2024Article
- Post-translational modifications in diabetic cardiomyopathy.Journal of cellular and molecular medicine · 2024Review
- The role of deubiquitinases in cardiac disease.Expert reviews in molecular medicine · 2024Review
- Upregulated PARP1 confers breast cancer resistance to CDK4/6 inhibitors via YB-1 phosphorylation.Experimental hematology & oncology · 2023Article
- Cx43 can form functional channels at the nuclear envelope and modulate gene expression in cardiac cells.Open biology · 2023Article
- APC ameliorates idiopathic membranous nephropathy by affecting podocyte apoptosis through the ERK1/2/YB-1/PLA2R1 axis.Molecular and cellular biochemistry · 2023Article
- Insights into SGLT2 inhibitor treatment of diabetic cardiomyopathy: focus on the mechanisms.Cardiovascular diabetology · 2023Review
- PARM1 Drives Smooth Muscle Cell Proliferation in Pulmonary Arterial Hypertension via AKT/FOXO3A Axis.International journal of molecular sciences · 2023Article
- OTUB1-mediated inhibition of ubiquitination: a growing list of effectors, multiplex mechanisms, and versatile functions.Frontiers in molecular biosciences · 2023Review
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Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Diabetic cardiomyopathy (DCM) is a major complication of diabetes, but its underlying mechanisms still remain unclear. The multifunctional protein Y-box binding protein-1 (YB-1) plays an important role in cardiac pathogenesis by regulating cardiac apoptosis, cardiac fibrosis, and pathological remodeling, whereas its role in chronic DCM requires further investigation. Here, we report that the phosphorylation of YB-1 at serine102 (S102) was markedly elevated in streptozotocin-induced diabetic mouse hearts and in high glucose-treated cardiomyocytes, whereas total YB-1 protein levels were significantly reduced. Coimmunoprecipitation experiments showed that YB-1 interacts with the deubiquitinase otubain-1, but hyperglycemia-induced phosphorylation of YB-1 at S102 diminished this homeostatic interaction, resulting in ubiquitination and degradation of YB-1. Mechanistically, the high glucose-induced phosphorylation of YB-1 at S102 is dependent on the upstream extracellular signal-regulated kinase (ERK)/Ras/mitogen-activated protein kinase (p90 ribosomal S6 kinase [RSK]) signaling pathway. Accordingly, pharmacological inhibition of the ERK pathway using the upstream kinase inhibitor U0126 ameliorated features of DCM compared with vehicle-treated diabetic mice. We demonstrate that ERK inhibition with U0126 also suppressed the phosphorylation of the downstream RSK and YB-1 (S102), which stabilized the interaction between YB-1 and otubain-1 and thereby preserved YB-1 protein expression in diabetic hearts. Taken together, we propose that targeting the ERK/RSK/YB-1 pathway could be a potential therapeutic approach for treating DCM.
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