ArticleCell cycle (Georgetown, Tex.)2016
STAR syndrome-associated CDK10/Cyclin M regulates actin network architecture and ciliogenesis.
Article in Cell cycle (Georgetown, Tex.), 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 42 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
- Phosphorylation at the Helm: Kinase-Mediated Regulation of Primary Cilia Assembly and Disassembly.Cytoskeleton (Hoboken, N.J.) · 2025Review
- EMT-ciliary signaling in quasi-mesenchymal-stem-like cells drives therapeutic resistance and is a druggable vulnerability in triple-negative breast cancer.EMBO molecular medicine · 2025Article
- Kinase activity of DYRK family members is required for regulating primary cilium length, stability and morphology.Communications biology · 2025Article
- CCDC66 regulation of cytoskeleton and cilia stability is important for signaling and epithelial organization.PLoS biology · 2025Article
- Illumination of understudied ciliary kinases.Frontiers in molecular biosciences · 2024Review
- Cyclin-dependent kinases: Masters of the eukaryotic universe.Wiley interdisciplinary reviews. RNA · 2023Review
- Primary cilia as dynamic and diverse signalling hubs in development and disease.Nature reviews. Genetics · 2023Review
- Mutually exclusive genetic interactions and gene essentiality shape the genomic landscape of primary melanoma.The Journal of pathology · 2023Article
- KSFinder-a knowledge graph model for link prediction of novel phosphorylated substrates of kinases.PeerJ · 2023Article
- Article
- Multimodal imaging of retinal findings in syndactyly, telecanthus, anogenital, and renal malformations (STAR) syndrome.American journal of ophthalmology case reports · 2022Article
- Functional characterization of the human Cdk10/Cyclin Q complex.Open biology · 2022Article
- Balancing the length of the distal tip by septins is key for stability and signalling function of primary cilia.The EMBO journal · 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
- Clinical and genetic heterogeneity of primary ciliopathies (Review).International journal of molecular medicine · 2021Review
- Cyclin-Dependent Kinases (CDK) and Their Role in Diseases Development-Review.International journal of molecular sciences · 2021Review
- The structure and function of protein kinase C-related kinases (PRKs).Biochemical Society transactions · 2021Review
Corrections and comments
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Authors and funding
8 authors at 5 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
CDK10/CycM is a protein kinase deficient in STAR (toe Syndactyly, Telecanthus and Anogenital and Renal malformations) syndrome, which results from mutations in the X-linked FAM58A gene encoding Cyclin M. The biological functions of CDK10/CycM and etiology of STAR syndrome are poorly understood. Here, we report that deficiency of CDK10/Cyclin M promotes assembly and elongation of primary cilia. We establish that this reflects a key role for CDK10/Cyclin M in regulation of actin network organization, which is known to govern ciliogenesis. In an unbiased screen, we identified the RhoA-associated kinase PKN2 as a CDK10/CycM phosphorylation substrate. We establish that PKN2 is a bone fide regulator of ciliogenesis, acting in a similar manner to CDK10/CycM. We discovered that CDK10/Cyclin M binds and phosphorylates PKN2 on threonines 121 and 124, within PKN2's core RhoA-binding domain. Furthermore, we demonstrate that deficiencies in CDK10/CycM or PKN2, or expression of a non-phosphorylatable version of PKN2, destabilize both the RhoA protein and the actin network architecture. Importantly, we established that ectopic expression of RhoA is sufficient to override the induction of ciliogenesis resulting from CDK10/CycM knockdown, indicating that RhoA regulation is critical for CDK10/CycM's negative effect on ciliogenesis. Finally, we show that kidney sections from a STAR patient display dilated renal tubules and abnormal, elongated cilia. Altogether, these results reveal CDK10/CycM as a key regulator of actin dynamics and a suppressor of ciliogenesis through phosphorylation of PKN2 and promotion of RhoA signaling. Moreover, they suggest that STAR syndrome is a ciliopathy.
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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.