ArticleProceedings of the National Academy of Sciences of the United States of America2013
CDK10/cyclin M is a protein kinase that controls ETS2 degradation and is deficient in STAR syndrome.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.
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49 citing papers in PubMed, 86 citations in OpenAlex.
- Cyclins and Cyclin-Dependent Kinases: Structure, Biological Functions, and Innovative Targeting Strategies in Cancer.MedComm · 2026Review
- CDK10 loss primes tumor cells for transcriptional vulnerability and sensitizes to CDK12/13 inhibition.Cell death & disease · 2026Article
- CDK10 suppresses nucleic acid sensors-mediated antitumor immunity.Nature cancer · 2026Article
- Uncovering the role of ETS2 in prostate cancer pathogenesis: relationship with p53 and ERG.Molecular biology reports · 2026Article
- Effect of Kinases in Extracellular Vesicles from HIV-1-Infected Cells on Bystander Cells.Cells · 2025Article
- Cyclin-dependent protein kinases and cell cycle regulation in biology and disease.Signal transduction and targeted therapy · 2025Review
- Illumination of understudied ciliary kinases.Frontiers in molecular biosciences · 2024Review
- Cyclin-dependent kinases: Masters of the eukaryotic universe.Wiley interdisciplinary reviews. RNA · 2023Review
- CMGC Kinases in Health and Cancer.Cancers · 2023Review
- CDK6 is activated by the atypical cyclin I to promote E2F-mediated gene expression and cancer cell proliferation.Molecular oncology · 2023Article
- Emerging approaches to CDK inhibitor development, a structural perspective.RSC chemical biology · 2023Article
- Discovery of CDK signature and CDK5 as potential biomarkers for predicting prognosis and immunotherapeutic response in gastric cancer peritoneal metastases.American journal of cancer research · 2023Article
- Transcription associated cyclin-dependent kinases as therapeutic targets for prostate cancer.Oncogene · 2022Review
- Functional characterization of the human Cdk10/Cyclin Q complex.Open biology · 2022Article
- An EMT-primary cilium-GLIS2 signaling axis regulates mammogenesis and claudin-low breast tumorigenesis.Science advances · 2021Article
- Functional characterization of CDK10 and cyclin M truncated variants causing severe developmental disorders.Molecular genetics & genomic medicine · 2021Article
- Identification of pathological transcription in autosomal dominant polycystic kidney disease epithelia.Scientific reports · 2021Article
- Ubiquitin-Mediated Control of ETS Transcription Factors: Roles in Cancer and Development.International journal of molecular sciences · 2021Review
- Targeting CDK9 for Anti-Cancer Therapeutics.Cancers · 2021Review
- Cyclin-Dependent Kinases (CDK) and Their Role in Diseases Development-Review.International journal of molecular sciences · 2021Review
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Authors and funding
10 authors at 6 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cyclin-dependent kinases (CDKs) regulate a variety of fundamental cellular processes. CDK10 stands out as one of the last orphan CDKs for which no activating cyclin has been identified and no kinase activity revealed. Previous work has shown that CDK10 silencing increases ETS2 (v-ets erythroblastosis virus E26 oncogene homolog 2)-driven activation of the MAPK pathway, which confers tamoxifen resistance to breast cancer cells. The precise mechanisms by which CDK10 modulates ETS2 activity, and more generally the functions of CDK10, remain elusive. Here we demonstrate that CDK10 is a cyclin-dependent kinase by identifying cyclin M as an activating cyclin. Cyclin M, an orphan cyclin, is the product of FAM58A, whose mutations cause STAR syndrome, a human developmental anomaly whose features include toe syndactyly, telecanthus, and anogenital and renal malformations. We show that STAR syndrome-associated cyclin M mutants are unable to interact with CDK10. Cyclin M silencing phenocopies CDK10 silencing in increasing c-Raf and in conferring tamoxifen resistance to breast cancer cells. CDK10/cyclin M phosphorylates ETS2 in vitro, and in cells it positively controls ETS2 degradation by the proteasome. ETS2 protein levels are increased in cells derived from a STAR patient, and this increase is attributable to decreased cyclin M levels. Altogether, our results reveal an additional regulatory mechanism for ETS2, which plays key roles in cancer and development. They also shed light on the molecular mechanisms underlying STAR syndrome.
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