ArticleMolecular cancer research : MCR2015
The Tumor Suppressor NKX3.1 Is Targeted for Degradation by DYRK1B Kinase.
Article in Molecular cancer research : MCR, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 20 citations in OpenAlex.
- Genetic Analysis of Osteosarcoma Cells in a 9-year-old Boy: Genes Involved in Cell Cycle Control.Acta medica academica · 2025Article
- Elevated expression levels of the protein kinase DYRK1B induce mesenchymal features in A549 lung cancer cells.BMC cancer · 2024Article
- Mirk/Dyrk1B Kinase Inhibitors in Targeted Cancer Therapy.Pharmaceutics · 2024Review
- KSFinder-a knowledge graph model for link prediction of novel phosphorylated substrates of kinases.PeerJ · 2023Article
- Reciprocal deregulation of NKX3.1 and AURKA axis in castration-resistant prostate cancer and NEPC models.Journal of biomedical science · 2021Article
- The Role of Nkx3.1 in Cancers and Stemness.International journal of stem cells · 2021Review
- Article
- Minibrain-related kinase/dual-specificity tyrosine-regulated kinase 1B implication in stem/cancer stem cells biology.World journal of stem cells · 2020Review
- CRISPR/Cas9-Mediated Point Mutation inCancer research · 2020Article
- Serum deprivation initiates adaptation and survival to oxidative stress in prostate cancer cells.Scientific reports · 2020Article
- Loss of PTEN Accelerates NKX3.1 Degradation to Promote Prostate Cancer Progression.Cancer research · 2019Article
- A facile consensus ranking approach enhances virtual screening robustness and identifies a cell-active DYRK1α inhibitor.Future medicinal chemistry · 2018Article
- Inferring Novel Tumor Suppressor Genes with a Protein-Protein Interaction Network and Network Diffusion Algorithms.Molecular therapy. Methods & clinical development · 2018Article
- NK3 homeobox 1 (NKX3.1) up-regulates forkhead box O1 expression in hepatocellular carcinoma and thereby suppresses tumor proliferation and invasion.The Journal of biological chemistry · 2017Article
- Identification and Functional Characterization of ST3GAL5 and ST8SIA1 Variants in Patients with Thyroid-Associated Ophthalmopathy.Yonsei medical journal · 2017Article
- NUDT2 Disruption Elevates Diadenosine Tetraphosphate (Ap4A) and Down-Regulates Immune Response and Cancer Promotion Genes.PloS one · 2016Article
- Longitudinal Study of DNA Methylation of Inflammatory Genes and Cancer Risk.Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology · 2015Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
unlabelledNKX3.1 is a prostate-specific homeodomain protein and tumor suppressor whose expression is reduced in the earliest phases of prostatic neoplasia. NKX3.1 expression is not only diminished by genetic loss and methylation, but the protein itself is a target for accelerated degradation caused by inflammation that is common in the aging prostate gland. NKX3.1 degradation is activated by phosphorylation at C-terminal serine residues that mediate ubiquitination and protein turnover. Because NKX3.1 is haploinsufficient, strategies to increase its protein stability could lead to new therapies. Here, a high-throughput screen was developed using an siRNA library for kinases that mediate NKX3.1 degradation. This approach identified several candidates, of which DYRK1B, a kinase that is subject to gene amplification and overexpression in other cancers, had the greatest impact on NKX3.1 half-life. Mechanistically, NKX3.1 and DYRK1B were shown to interact via the DYRK1B kinase domain. In addition, an in vitro kinase assay showed that DYRK1B phosphorylated NKX3.1 at serine 185, a residue critical for NKX3.1 steady-state turnover. Lastly, small-molecule inhibitors of DYRK1B prolonged NKX3.1 half-life. Thus, DYRK1B is a target for enzymatic inhibition in order to increase cellular NKX3.1. IMPLICATIONS: DYRK1B is a promising and novel kinase target for prostate cancer treatment mediated by enhancing NKX3.1 levels.
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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.