ArticleThe Journal of biological chemistry2011
CRM1 protein-mediated regulation of nuclear clusterin (nCLU), an ionizing radiation-stimulated, Bax-dependent pro-death factor.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 40 citations in OpenAlex.
- Elucidating the function of clusterin in the progression of diabetic kidney disease.Frontiers in pharmacology · 2025Review
- Review
- Clusterin: a double-edged sword in cancer and neurological disorders.EXCLI journal · 2024Review
- A novel coiled-coil domain containing-related gene signature for predicting prognosis and treatment effect of breast cancer.Journal of cancer research and clinical oncology · 2023Article
- Cisplatin Dependent Secretion of Immunomodulatory High Mobility Group Box 1 (HMGB1) Protein from Lung Cancer Cells.Biomolecules · 2023Article
- The Ins and Outs of Clusterin: Its Role in Cancer, Eye Diseases and Wound Healing.International journal of molecular sciences · 2023Review
- The Nuclear Transporter Importin 13 Can Regulate Stress-Induced Cell Death through the Clusterin/KU70 Axis.Cells · 2023Article
- The Influence of Clusterin Glycosylation Variability on Selected Pathophysiological Processes in the Human Body.Oxidative medicine and cellular longevity · 2022Review
- Clusterin and Its Role in Insulin Resistance and the Cardiometabolic Syndrome.Frontiers in immunology · 2021Review
- Function, clinical application, and strategies of Pre-mRNA splicing in cancer.Cell death and differentiation · 2019Review
- Clusterin Impairs Hepatic Insulin Sensitivity and Adipocyte Clusterin Associates With Cardiometabolic Risk.Diabetes care · 2019Article
- Clusterin in Alzheimer's Disease: Mechanisms, Genetics, and Lessons From Other Pathologies.Frontiers in neuroscience · 2019Review
- DNA methylation analysis on purified neurons and glia dissects age and Alzheimer's disease-specific changes in the human cortex.Epigenetics & chromatin · 2018Article
- Clusterin: Review of research progress and looking ahead to direction in hepatocellular carcinoma.World journal of gastroenterology · 2015Review
- Nucleofection of rat pheochromocytoma PC-12 cells with human mutated beta-amyloid precursor protein gene (APP-sw) leads to reduced viability, autophagy-like process, and increased expression and secretion of beta amyloid.BioMed research international · 2015Article
- Involvement of chromosome region maintenance 1 (CRM1) in the formation and progression of esophageal squamous cell carcinoma.Medical oncology (Northwood, London, England) · 2014Article
- The physiological roles of apolipoprotein J/clusterin in metabolic and cardiovascular diseases.Reviews in endocrine & metabolic disorders · 2014Review
- Influenza A virus nucleoprotein induces apoptosis in human airway epithelial cells: implications of a novel interaction between nucleoprotein and host protein Clusterin.Cell death & disease · 2013Article
- Secretory clusterin contributes to oxaliplatin resistance by activating Akt pathway in hepatocellular carcinoma.Cancer science · 2013Article
- Article
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Authors and funding
9 authors at 4 institutions in 2 countries.
Funding
Abstract
Expression of the clusterin (CLU) gene results in the synthesis of a conventional secretory isoform set (pre- and mature secretory clusterin proteins, psCLU/sCLU), as well as another set of intracellular isoforms, appearing in the cytoplasm (pre-nuclear CLU, pnCLU) and in the nucleus as an ∼55-kDa mature nuclear clusterin (nCLU) form. These two isoform sets have opposing cell functions: pro-survival and pro-death, respectively. Although much is known about the regulation and function of sCLU as a pro-survival factor, the regulation and function of endogenous nCLU in cell death are relatively unexplored. Here, we show that depletion of endogenous nCLU protein using siRNA specific to its truncated mRNA increased clonogenic survival of ionizing radiation (IR)-exposed cells. nCLU-mediated apoptosis was Bax-dependent, and lethality correlated with accumulation of mature nCLU protein. nCLU accumulation was regulated by CRM1 because binding between CRM1 and nCLU proteins was significantly diminished by leptomycin B (LMB), and nuclear levels of nCLU protein were significantly enhanced by LMB and IR co-treatment. Moreover, LMB treatment significantly enhanced IR-induced nCLU-mediated cell death responses. Importantly, bax(-/-) and bax(-/-)/bak(-/-) double knock-out cells were resistant to nCLU-mediated cell death, whereas bak(-/-) or wild-type bax(+/+)/bak(+/+) cells were hypersensitive. The regulation of nCLU by CRM1 nuclear export/import may explain recent clinical results showing that highly malignant tumors have lost the ability to accumulate nCLU levels, thereby avoiding growth inhibition and cell death.
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Registered trials
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.