| http://purl.uniprot.org/citations/32701505 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/32701505 | http://www.w3.org/2000/01/rdf-schema#comment | "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."xsd:string |
| http://purl.uniprot.org/citations/32701505 | http://purl.org/dc/terms/identifier | "doi:10.1172/jci134217"xsd:string |
| http://purl.uniprot.org/citations/32701505 | http://purl.uniprot.org/core/author | "Muller A."xsd:string |
| http://purl.uniprot.org/citations/32701505 | http://purl.uniprot.org/core/author | "Dickmanns A."xsd:string |
| http://purl.uniprot.org/citations/32701505 | http://purl.uniprot.org/core/author | "Schulze-Osthoff K."xsd:string |
| http://purl.uniprot.org/citations/32701505 | http://purl.uniprot.org/core/author | "Kramer D."xsd:string |
| http://purl.uniprot.org/citations/32701505 | http://purl.uniprot.org/core/author | "Dobbelstein M."xsd:string |
| http://purl.uniprot.org/citations/32701505 | http://purl.uniprot.org/core/author | "Hailfinger S."xsd:string |
| http://purl.uniprot.org/citations/32701505 | http://purl.uniprot.org/core/author | "Resch C."xsd:string |
| http://purl.uniprot.org/citations/32701505 | http://purl.uniprot.org/core/author | "Schakel K."xsd:string |
| http://purl.uniprot.org/citations/32701505 | http://purl.uniprot.org/core/date | "2020"xsd:gYear |
| http://purl.uniprot.org/citations/32701505 | http://purl.uniprot.org/core/name | "J Clin Invest"xsd:string |
| http://purl.uniprot.org/citations/32701505 | http://purl.uniprot.org/core/pages | "5765-5781"xsd:string |
| http://purl.uniprot.org/citations/32701505 | http://purl.uniprot.org/core/title | "The CDK4/6-EZH2 pathway is a potential therapeutic target for psoriasis."xsd:string |
| http://purl.uniprot.org/citations/32701505 | http://purl.uniprot.org/core/volume | "130"xsd:string |
| http://purl.uniprot.org/citations/32701505 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/32701505 |
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