ArticleOncogene2018
KPNB1 inhibition disrupts proteostasis and triggers unfolded protein response-mediated apoptosis in glioblastoma cells.
Article in Oncogene, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers, 1 of them a synthesis that pooled it.
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Who cites it
36 citing papers in PubMed, 1 synthesis or guideline pooled it, 72 citations in OpenAlex.
- Gene network profiling in muscle-invasive bladder cancer: A systematic review and meta-analysis.Urologic oncology · 2022Pooled it
- Current therapeutic interventions to target cancer stem cells for metastasis.International journal of clinical oncology · 2026Review
- Therapeutic Approaches Interfering with Nuclear Localization Signals: An Emerging Strategy for CNS-Related Diseases.Current neuropharmacology · 2026Review
- The function of PCSK9 in doxorubicin-induced cardiotoxicity and its underlying mechanism.Scientific reports · 2025Article
- Review
- VCP's nuclear journey: Initiated by interacting with KPNB1 to repair DNA damage.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Recent Insights into the Angioregulatory Role of Long Non-coding RNAs and Circular RNAs in Gliomas: From Signaling Pathways to Clinical Aspects.Current medicinal chemistry · 2025Review
- KPNB1-ATF4 induces BNIP3-dependent mitophagy to drive odontoblastic differentiation in dental pulp stem cells.Cellular & molecular biology letters · 2024Article
- Article
- Astragaloside Ⅳ mediates the effect and mechanism of KPNB1 on biological behavior and tumor growth in prostate cancer.Heliyon · 2024Article
- Survival-Related Genes on Chromosomes 6 and 17 in Medulloblastoma.International journal of molecular sciences · 2024Article
- Clinical significance of CD166 and HER-2 in different types of gastric cancer.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2024Article
- Stabilization of KPNB1 by deubiquitinase USP7 promotes glioblastoma progression through the YBX1-NLGN3 axis.Journal of experimental & clinical cancer research : CR · 2024Article
- Therapeutic targeting of nuclear export and import receptors in cancer and their potential in combination chemotherapy.IUBMB life · 2024Review
- ADAMTS-1 has nuclear localization in cells with epithelial origin and leads to decreased cell migration.Experimental cell research · 2023Article
- MicroRNA-130a-3p impedes the progression of papillary thyroid carcinoma through downregulation of KPNB1 by targeting PSME3.Endocrine · 2023Article
- Epigenetic silencing of HTATIP2 in glioblastoma contributes to treatment resistance by enhancing nuclear translocation of the DNA repair protein MPG.Molecular oncology · 2023Article
- Article
- Tumor-promoting properties of karyopherin β1 in melanoma by stabilizing Ras-GTPase-activating protein SH3 domain-binding protein 1.Cancer gene therapy · 2022Article
- Inhibition of Karyopherin β1-Mediated Nuclear Import Disrupts Oncogenic Lineage-Defining Transcription Factor Activity in Small Cell Lung Cancer.Cancer research · 2022Article
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The nuclear import receptor karyopherin β1 (KPNB1) is involved in the nuclear import of most proteins and in the regulation of multiple mitotic events. Upregulation of KPNB1 has been observed in cancers including glioblastoma. Depletion of KPNB1 induces mitotic arrest and apoptosis in cancer cells, but the underlying mechanism is not clearly elucidated. Here, we found that downregulation and functional inhibition of KPNB1 in glioblastoma cells induced growth arrest and apoptosis without apparent mitotic arrest. KPNB1 inhibition upregulated Puma and Noxa and freed Mcl-1-sequestered Bax and Bak, leading to mitochondrial outer membrane permeabilization (MOMP) and apoptosis. Moreover, combination of Bcl-xL inhibitors and KPNB1 inhibition enhanced apoptosis in glioblastoma cells. KPNB1 inhibition promoted cytosolic retention of its cargo and impaired cellular proteostasis, resulting in elevated polyubiquitination, formation of aggresome-like-induced structure (ALIS), and unfolded protein response (UPR). Ubiquitination elevation and UPR activation in KPNB1-deficient cells were reversed by KPNB1 overexpression or inhibitors of protein synthesis but aggravated by inhibitors of autophagy-lysosome or proteasome, indicating that rebalance of cytosolic/nuclear protein distribution and alleviation of protein overload favor proteostasis and cell survival. Chronic activation of eIF2α/ATF4 cascade of UPR was responsible for the upregulation of Puma and Noxa, apoptosis and ABT-263 sensitivity. Taken together, our findings demonstrate that KPNB1 is required for proteostasis maintenance and its inhibition induces apoptosis in glioblastoma cells through UPR-mediated deregulation of Bcl-2 family members.
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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.