ArticleThe Journal of clinical investigation2020
The CDK4/6-EZH2 pathway is a potential therapeutic target for psoriasis.
Article in The Journal of clinical investigation, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 58 citations in OpenAlex.
- Keratinocyte-specific STAT3 knockout attenuates imiquimod-induced psoriasiform phenotype in mice.Experimental animals · 2026Article
- Inhibiting cyclin D1-CDK6 suppresses senescence-associated inflammatory gene expression and age-related functional decline.Nature aging · 2026Article
- Disruption of CDK4/6-RARα-NF-κB axis attenuates senescence-associated inflammation and improves function during aging and following chemotherapy.Nature aging · 2026Article
- Olive (Olea europaea) phenolics for the control of psoriasis via targeting SMYD2 and IL-17A protein-protein interaction networks.Journal of natural medicines · 2026Article
- Targeting EZH2 in autoimmune diseases: unraveling epigenetic regulation and therapeutic potential.Naunyn-Schmiedeberg's archives of pharmacology · 2025Review
- Constitutive expression of the transcriptional co-activator IκBζ promotes melanoma growth and immunotherapy resistance.Nature communications · 2025Article
- Drug repurposing of cyclin-dependent kinase inhibitors for neutrophilic acute respiratory distress syndrome and psoriasis.Journal of advanced research · 2025Review
- QingReDu capsule ameliorates psoriasis vulgaris by regulating EZH2/NF-κB signaling pathway.Archives of dermatological research · 2025Article
- Cyclin-dependent protein kinases and cell cycle regulation in biology and disease.Signal transduction and targeted therapy · 2025Review
- Syndrome Differentiation and Treatment of Psoriasis by Traditional Chinese Medicines: An Integrating Study of Multi-Omics Analysis and Experimental Validation.Journal of inflammation research · 2025Article
- Ribociclib leverages phosphodiesterase 4 inhibition in the treatment of neutrophilic inflammation and acute respiratory distress syndrome.Journal of advanced research · 2024Article
- SUMO E3 ligase MUL1 inhibits lymph node metastasis of bladder cancer by mediating mitochondrial HSPA9 translocation.International journal of biological sciences · 2024Article
- Strategy of combining CDK4/6 inhibitors with other therapies and mechanisms of resistance.International journal of clinical and experimental pathology · 2024Review
- Reactive oxygen species-responsive supramolecular deucravacitinib self-assembly polymer micelles alleviate psoriatic skin inflammation by reducing mitochondrial oxidative stress.Frontiers in immunology · 2024Article
- Signaling pathways and targeted therapies for psoriasis.Signal transduction and targeted therapy · 2023Review
- The Therapeutic Potential of CDK4/6 Inhibitors, Novel Cancer Drugs, in Kidney Diseases.International journal of molecular sciences · 2023Review
- The roles of EZH2 in cancer and its inhibitors.Medical oncology (Northwood, London, England) · 2023Review
- The BRD4 inhibitor JQ1 augments the antitumor efficacy of abemaciclib in preclinical models of gastric carcinoma.Journal of experimental & clinical cancer research : CR · 2023Article
- IL-17A-driven psoriasis is critically dependent on IL-36 signaling.Frontiers in immunology · 2023Article
- Gene set enrichment analysis and ingenuity pathway analysis to verify the impact of Wnt signaling in psoriasis treated with Taodan granules.American journal of translational research · 2023Article
Corrections and comments
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Authors and funding
8 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Psoriasis is a frequent, inflammatory skin disease characterized by keratinocyte hyperproliferation and a disease-related infiltration of immune cells. Here, we identified a novel proinflammatory signaling pathway driven by cyclin-dependent kinase 4 (CDK4) and CDK6 and the methyltransferase EZH2 as a valid target for psoriasis therapy. Delineation of the pathway revealed that CDK4/6 phosphorylated EZH2 in keratinocytes, thereby triggering a methylation-induced activation of STAT3. Subsequently, active STAT3 resulted in the induction of IκBζ, which is a key proinflammatory transcription factor required for cytokine synthesis in psoriasis. Pharmacological or genetic inhibition of CDK4/6 or EZH2 abrogated psoriasis-related proinflammatory gene expression by suppressing IκBζ induction in keratinocytes. Importantly, topical application of CDK4/6 or EZH2 inhibitors on the skin was sufficient to fully prevent the development of psoriasis in various mouse models by suppressing STAT3-mediated IκBζ expression. Moreover, we found a hyperactivation of the CDK4/6-EZH2 pathway in human and mouse psoriatic skin lesions. Thus, this study not only identifies a novel psoriasis-relevant proinflammatory pathway, but also proposes the repurposing of CDK4/6 or EZH2 inhibitors as a new therapeutic option for patients with psoriasis.
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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.