ArticleCell death & disease2012
Targeting β-tubulin:CCT-β complexes incurs Hsp90- and VCP-related protein degradation and induces ER stress-associated apoptosis by triggering capacitative Ca2+ entry, mitochondrial perturbation and caspase overactivation.
Article in Cell death & disease, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
15 citing papers in PubMed, 28 citations in OpenAlex.
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- Revisiting the chaperonin T-complex protein-1 ring complex in human health and disease: A proteostasis modulator and beyond.Clinical and translational medicine · 2024Review
- Quantitative analysis of acetylation in peste des petits ruminants virus-infected Vero cells.Virology journal · 2023Article
- FACS-based genome-wide CRISPR screens define key regulators of DNA damage signaling pathways.Molecular cell · 2023Article
- TgMORN2, a MORN Family Protein Involved in the Regulation of Endoplasmic Reticulum Stress inInternational journal of molecular sciences · 2023Article
- Chronic Cerebral Hypoperfusion-Induced Disturbed Proteostasis of Mitochondria and MAM Is Reflected in the CSF of Rats by Proteomic Analysis.Molecular neurobiology · 2023Article
- Chaperonin containing TCP-1 (CCT/TRiC) is a novel therapeutic and diagnostic target for neuroblastoma.Frontiers in oncology · 2022Article
- LncRNA LINC00460 takes a stimulating role on hepatocellular carcinoma stemness property.Cell cycle (Georgetown, Tex.) · 2021Article
- Article
- Mutation in the Zebrafish cct2 Gene Leads to Abnormalities of Cell Cycle and Cell Death in the Retina: A Model of CCT2-Related Leber Congenital Amaurosis.Investigative ophthalmology & visual science · 2018Article
- Clofoctol and sorafenib inhibit prostate cancer growth via synergistic induction of endoplasmic reticulum stress and UPR pathways.Cancer management and research · 2018Article
- Targeting chaperonin containing TCP1 (CCT) as a molecular therapeutic for small cell lung cancer.Oncotarget · 2017Article
- Disrupting CCT-β : β-tubulin selectively kills CCT-β overexpressed cancer cells through MAPKs activation.Cell death & disease · 2017Article
- A TRPV1-to-secretagogin regulatory axis controls pancreatic β-cell survival by modulating protein turnover.The EMBO journal · 2017Article
- Targeting the XIAP/caspase-7 complex selectively kills caspase-3-deficient malignancies.The Journal of clinical investigation · 2013Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
We have previously demonstrated that interrupting the protein-protein interaction (PPI) of β-tubulin:chaperonin-containing TCP-1β (CCT-β) induces the selective killing of multidrug-resistant cancer cells due to CCT-β overexpression. However, the molecular mechanism has not yet been identified. In this study, we found that CCT-β interacts with a myriad of intracellular proteins involved in the cellular functions of the endoplasmic reticulum (ER), mitochondria, cytoskeleton, proteasome and apoptosome. Our data show that the targeted cells activate both the heat-shock protein 90 (Hsp90)-associated protein ubiquitination/degradation pathway to eliminate misfolded proteins in the cytoplasm and the valosin-containing protein (VCP)-centered ER-associated protein degradation pathway to reduce the excessive levels of unfolded polypeptides from the ER, thereby mitigating ER stress, at the onset of β-tubulin:CCT-β complex disruption. Once ER stress is expanded, ER stress-associated apoptotic signaling is enforced, as exhibited by cellular vacuolization and intracellular Ca2+ release. Furthermore, the elevated intracellular Ca2+ levels resulting from capacitative Ca2+ entry augments apoptotic signaling by provoking mitochondrial perturbation and caspase overactivation in the targeted cells. These findings not only provide a detailed picture of the apoptotic signaling cascades evoked by targeting the β-tubulin:CCT-β complex but also demonstrate a strategy to combat malignancies with chemoresistance to Hsp90- and VCP-related anticancer agents.
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