ArticleCell cycle (Georgetown, Tex.)2012
HER2-Akt signaling in regulating COP9 signalsome subunit 6 and p53.
Article in Cell cycle (Georgetown, Tex.), 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 33 citations in OpenAlex.
- Article
- COPS6 promotes tumor progression and reduces CD8Acta pharmacologica Sinica · 2023Article
- Tespa1 facilitates hematopoietic and leukemic stem cell maintenance by restricting c-Myc degradation.Leukemia · 2023Article
- CSN6 promotes melanoma proliferation and metastasis by controlling the UBR5-mediated ubiquitination and degradation of CDK9.Cell death & disease · 2021Article
- EGF Relays Signals to COP1 and Facilitates FOXO4 Degradation to Promote Tumorigenesis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2020Article
- CSN6: a promising target for cancer prevention and therapy.Histology and histopathology · 2020Review
- CSN6-TRIM21 axis instigates cancer stemness during tumorigenesis.British journal of cancer · 2020Article
- CSN6 promotes tumorigenesis of gastric cancer by ubiquitin-independent proteasomal degradation of p16Cancer biology & medicine · 2019Article
- CSN6 expression is associated with pancreatic cancer progression and predicts poor prognosis.Cancer biology & therapy · 2019Article
- Quercetin-induced apoptosis of HT-29 colon cancer cells via inhibition of the Akt-CSN6-Myc signaling axis.Molecular medicine reports · 2016Article
- Bioorthogonal two-component drug delivery in HER2(+) breast cancer mouse models.Scientific reports · 2016Article
- The Role of the COP9 Signalosome and Neddylation in DNA Damage Signaling and Repair.Biomolecules · 2015Review
- Article
- ERK2-Dependent Phosphorylation of CSN6 Is Critical in Colorectal Cancer Development.Cancer cell · 2015Article
- Article
- CSN6 positively regulates c-Jun in a MEKK1-dependent manner.Cell cycle (Georgetown, Tex.) · 2015Article
- Regulating the stability and localization of CDK inhibitor p27(Kip1) via CSN6-COP1 axis.Cell cycle (Georgetown, Tex.) · 2015Article
- CSN6 drives carcinogenesis by positively regulating Myc stability.Nature communications · 2014Article
- The COP9 signalosome subunit 6 (CSN6): a potential oncogene.Cell division · 2013Article
- CDK inhibitor p57 (Kip2) is downregulated by Akt during HER2-mediated tumorigenicity.Cell cycle (Georgetown, Tex.) · 2013Article
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Authors and funding
12 authors at 3 institutions in 3 countries.
Funding
Abstract
HER2/neu oncogene is frequently overexpressed in various types of cancer, and the (PI3K)-Akt signaling pathway is often activated in HER2-overexpressing cancer cells. CSN6, subunit 6 of the COP9 signalosome complex, is pivotal in regulating MDM2 to destabilize p53, but its upstream regulators remain unclear. Here we show that the HER2-Akt axis is linked to CSN6 regulation, and that Akt is a positive regulator of CSN6. Ectopic expression of Akt can increase the expression of CSN6; accordingly, Akt inhibition leads to CSN6 destabilization. Mechanistic studies show that Akt causes CSN6 phosphorylation at Ser 60, which, in turn, reduces ubiquitin-mediated protein degradation of CSN6. Significantly, Akt's positive impact on CSN6 elevation translates into p53 degradation, potentiating transformational activity and increasing DNA damage. Akt inhibition can attenuate these defects caused by CSN6. These data suggest that Akt is an important positive regulator of CSN6, and that activation of Akt in many types of cancer could lead to abnormal elevation of CSN6 and result in downregulated p53 and increased DNA damage, which promotes cancer cell growth.
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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.