ArticleClinical and translational medicine2022
Ubiquitylation of cyclin C by HACE1 regulates cisplatin-associated sensitivity in gastric cancer.
Article in Clinical and translational medicine, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers, 1 of them a synthesis that pooled it.
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13 citing papers in PubMed, 1 synthesis or guideline pooled it, 15 citations in OpenAlex.
- The molecular mechanisms of mitochondrial dynamics and mitophagy and their complex association with cancer drug resistance.Journal of translational medicine · 2025Pooled it
- HSP90/PUS7/THUMPD1 promotes metastasis and cisplatin resistance in gastric cancer cells.Scientific reports · 2025Article
- Article
- The role of mitochondrial biogenesis, mitochondrial dynamics and mitophagy in gastrointestinal tumors.Cancer cell international · 2025Review
- Implication of protein post translational modifications in gastric cancer.Frontiers in cell and developmental biology · 2025Review
- HACE1 as a bridge between oxidative stress and autophagy.Frontiers in immunology · 2025Review
- Whole-exome profiles of inflammatory breast cancer and pathological response to neoadjuvant chemotherapy.Journal of translational medicine · 2024Article
- Structural Basis for the Enzymatic Activity of the HACE1 HECT-Type E3 Ligase Through N-Terminal Helix Dimerization.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
- The Regulation of Cyclins and Cyclin-Dependent Kinases in the Development of Gastric Cancer.International journal of molecular sciences · 2023Review
- Emerging roles of the HECT E3 ubiquitin ligases in gastric cancer.Pathology oncology research : POR · 2023Review
- HACE1 builds molecular crosstalks between rare diseases and (more) common disorders.Clinical and translational medicine · 2022Article
- Cyclin C: A new responser for chemosensitivity in cancer.Clinical and translational medicine · 2022Article
- Ubiquitylation of cyclin C by HACE1 regulates cisplatin-associated sensitivity in gastric cancer.Clinical and translational medicine · 2022Article
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8 authors at 2 institutions in 1 country.
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No grant is acknowledged in the PubMed record.
Abstract
backgroundCyclin C (CCNC) was reported to take part in regulating mitochondria-derived oxidative stress under cisplatin stimulation. However, its effect in gastric cancer is unknown. This study aimed to investigate the role of cyclin C and its ubiquitylation in regulating cisplatin resistance in gastric cancer.
methodsThe interaction between HECT domain and ankyrin repeat-containing E3 ubiquitin-protein ligase 1 (HACE1) and cyclin C was investigated by GST pull-down assay, co-immunoprecipitation and ubiquitylation assay. Mitochondria-derived oxidative stress was studied by MitoSOX Red assay, seahorse assay and mitochondrial membrane potential measurement. Cyclin C-associated cisplatin resistance was studied in vivo via xenograft.
resultsHACE1 catalysed the ubiquitylation of cyclin C by adding Lys11-linked ubiquitin chains when cyclin C translocates to cytoplasm induced by cisplatin treatment. The ubiquitin-modified cyclin C then anchor at mitochondira, which induced mitochondrial fission and ROS synthesis. Depleting CCNC or mutation on the ubiquitylation sites decreased mitochondrial ROS production and reduced cell apoptosis under cisplatin treatment. Xenograft study showed that disrupting cyclin C ubiquitylation by HACE1 conferred impairing cell apoptosis response upon cisplatin administration.
conclusionsCyclin C is a newly identified substrate of HACE1 E3 ligase. HACE1-mediated ubiquitylation of cyclin C sheds light on a better understanding of cisplatin-associated resistance in gastric cancer patients. Ubiquitylation of cyclin C by HACE1 regulates cisplatin-associated sensitivity in gastric cancer. With cisplatin-induced nuclear-mitochondrial translocation of cyclin C, its ubiquitylation by HACE1 increased mitochondrial fission and mitochondrial-derived oxidative stress, leading to cell apoptosis.
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