ArticleOncogene2015
Cables1 controls p21/Cip1 protein stability by antagonizing proteasome subunit alpha type 3.
Article in Oncogene, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 45 citations in OpenAlex.
- Subcellular compartmentalization dependent dichotomy of p21 in cancer.Molecular biology reports · 2026Review
- The Emerging Role of p21 in Diabetes and Related Metabolic Disorders.International journal of molecular sciences · 2024Review
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- Epigenomic and Transcriptomic Prioritization of Candidate Obesity-Risk Regulatory GWAS SNPs.International journal of molecular sciences · 2022Article
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- Characterization of a bicistronic knock-in reporter mouse model for investigating the role of CABLES2 in vivo.Experimental animals · 2021Article
- Role of Curcumin in Regulating Long Noncoding RNA Expression in Cancer.Advances in experimental medicine and biology · 2021Article
- PAH-pollution effects on sensitive and resistant embryos: Integrating structure and function with gene expression.PloS one · 2021Article
- LC-MS/MS-Based Quantitative Proteomics Analysis of Different Stages of Non-Small-Cell Lung Cancer.BioMed research international · 2021Article
- Atypical cyclins: the extended family portrait.Cellular and molecular life sciences : CMLS · 2020Review
- N-myc downstream-regulated gene 1 inhibits the proliferation of colorectal cancer through emulative antagonizing NEDD4-mediated ubiquitylation of p21.Journal of experimental & clinical cancer research : CR · 2019Article
- CABLES1 Deficiency Impairs Quiescence and Stress Responses of Hematopoietic Stem Cells in Intrinsic and Extrinsic Manners.Stem cell reports · 2019Article
- The targeting of non‑coding RNAs by curcumin: Facts and hopes for cancer therapy (Review).Oncology reports · 2019Review
- Targeting TF-AKT/ERK-EGFR Pathway Suppresses the Growth of Hepatocellular Carcinoma.Frontiers in oncology · 2019Article
- Deubiquitylation and stabilization of p21 by USP11 is critical for cell-cycle progression and DNA damage responses.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- YM155 enhances docetaxel efficacy in ovarian cancer.American journal of translational research · 2018Article
- Cyclin-dependent kinase 7 inhibitor THZ2 inhibits the growth of human gastric cancerAmerican journal of translational research · 2018Article
- Structure Identification and In Vitro Anticancer Activity of Lathyrol-3-phenylacetate-5,15-diacetate.Molecules (Basel, Switzerland) · 2017Article
- Loss-of-function mutations in theEndocrine-related cancer · 2017Article
- Caragaphenol a induces reactive oxygen species related apoptosis in human gastric cancer cells.American journal of translational research · 2017Article
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
The cyclin-dependent kinase (CDK) inhibitor 1A, p21/Cip1, is a vital cell cycle regulator, dysregulation of which has been associated with a large number of human malignancies. One critical mechanism that controls p21 function is through its degradation, which allows the activation of its associated cell cycle-promoting kinases, CDK2 and CDK4. Thus delineating how p21 is stabilized and degraded will enhance our understanding of cell growth control and offer a basis for potential therapeutic interventions. Here we report a novel regulatory mechanism that controls the dynamic status of p21 through its interaction with Cdk5 and Abl enzyme substrate 1 (Cables1). Cables1 has a proposed role as a tumor suppressor. We found that upregulation of Cables1 protein was correlated with increased half-life of p21 protein, which was attributed to Cables1/p21 complex formation and supported by their co-localization in the nucleus. Mechanistically, Cables1 interferes with the proteasome (Prosome, Macropain) subunit alpha type 3 (PSMA3) binding to p21 and protects p21 from PSMA3-mediated proteasomal degradation. Moreover, silencing of p21 partially reverses the ability of Cables1 to induce cell death and inhibit cell proliferation. In further support of a potential pathophysiological role of Cables1, the expression level of Cables1 is tightly associated with p21 in both cancer cell lines and human lung cancer patient tumor samples. Together, these results suggest Cables1 as a novel p21 regulator through maintaining p21 stability and support the model that the tumor-suppressive function of Cables1 occurs at least in part through enhancing the tumor-suppressive activity of p21.
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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.