ArticleCell cycle (Georgetown, Tex.)2012
CDK inhibitor p57 (Kip2) is negatively regulated by COP9 signalosome subunit 6.
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, 32 citations in OpenAlex.
- Friend or foe? Reciprocal regulation between E3 ubiquitin ligases and deubiquitinases.Biochemical Society transactions · 2024Review
- The Involvement of Ubiquitination Machinery in Cell Cycle Regulation and Cancer Progression.International journal of molecular sciences · 2021Review
- CSN6 promotes melanoma proliferation and metastasis by controlling the UBR5-mediated ubiquitination and degradation of CDK9.Cell death & disease · 2021Article
- CSN6: a promising target for cancer prevention and therapy.Histology and histopathology · 2020Review
- CSN6 promotes the cell migration of breast cancer cells by positively regulating Snail1 stability.International journal of medical sciences · 2020Observational
- 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
- COP9 signalosome subunit CSN5, but not CSN6, is upregulated in lung adenocarcinoma and predicts poor prognosis.Journal of thoracic disease · 2018Article
- Downregulation of CSN6 attenuates papillary thyroid carcinoma progression by reducing Wnt/β-catenin signaling and sensitizes cancer cells to FH535 therapy.Cancer medicine · 2018Article
- 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
- Mutations in the PCNA-binding site of CDKN1C inhibit cell proliferation by impairing the entry into S phase.Cell division · 2015Article
- Regulating the stability and localization of CDK inhibitor p27(Kip1) via CSN6-COP1 axis.Cell cycle (Georgetown, Tex.) · 2015Article
- The COP9 signalosome and vascular function: intriguing possibilities?American journal of cardiovascular disease · 2015Review
- CSN6 drives carcinogenesis by positively regulating Myc stability.Nature communications · 2014Article
- Longikaurin A, a natural ent-kaurane, induces G2/M phase arrest via downregulation of Skp2 and apoptosis induction through ROS/JNK/c-Jun pathway in hepatocellular carcinoma cells.Cell death & disease · 2014Article
- Dynamic regulation of the COP9 signalosome in response to DNA damage.Molecular and cellular biology · 2014Article
- The COP9 signalosome subunit 6 (CSN6): a potential oncogene.Cell division · 2013Article
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Authors and funding
16 authors at 4 institutions in 3 countries.
Funding
Abstract
Subunit 6 of the COP9 signalosome complex, CSN6, is known to be critical to the regulation of the MDM2-p53 axis for cell proliferation and anti-apoptosis, but its many targets remain unclear. Here we show that p57 (Kip2) is a target of CSN6, and that CSN6 is a negative regulator of p57 (Kip2) . CSN6 associates with p57 (Kip2) , and its overexpression can decrease the steady-state expression of p57 (Kip2) ; accordingly, CSN6 deficiency leads to p57 (Kip2) stabilization. Mechanistic studies show that CSN6 associates with p57 (Kip2) and Skp2, a component of the E3 ligase, which, in turn, facilitates Skp2-mediated protein ubiquitination of p57 (Kip2) . Loss of Skp2 compromised CSN6-mediated p57 (Kip2) destabilization, suggesting collaboration between Skp2 and CSN6 in degradation of p57 (Kip2) . CSN6's negative impact on p57 (Kip2) elevation translates into cell growth promotion, cell cycle deregulation and potentiated transformational activity. Significantly, univariate Kaplan-Meier analysis of tumor samples demonstrates that high CSN6 expression or low p57 expression is associated with poor overall survival. These data suggest that CSN6 is an important negative regulator of p57 (Kip2) , and that overexpression of CSN6 in many types of cancer could lead to decreased expression of p57 (Kip2) and result in promoted cancer cell growth.
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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.