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Aurora kinases are Ser/Thr-directed protein kinases which play pivotal roles in mitosis. Recent evidences highlight the importance of these kinases in multiple biological events including skeletal muscle differentiation. Our earlier study identified the transcription factor POU6F1 (or mPOU) as a novel Aurora kinase (Aurk) A substrate. Here, we report that Aurora kinase A phosphorylates mPOU at Ser197 and inhibit its DNA-binding ability. Delving into mPOU physiology, we find that the phospho-mimic (S197D) mPOU mutant exhibits enhancement, while the wild type or the phospho-deficient mutant shows retardation in C2C12 myoblast differentiation. Interestingly, POU6F1 depletion phenocopies S197D-mPOU overexpression in the differentiation context. Collectively, our results signify mPOU as a negative regulator of skeletal muscle differentiation and strengthen the importance of AurkA in skeletal myogenesis.
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http://dx.doi.org/10.1093/jb/mvz088 | DOI Listing |
Biomed Pharmacother
September 2025
Department of Medical Genetics, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
Polyploidy, a conserved mechanism involved in normal development and tissue homeostasis, plays a paradoxical role in cancer by facilitating both tumor progression and therapeutic vulnerability. Although polyploidization may confer survival advantages to cancer cells, its controlled induction could represent an effective anticancer strategy. Aurora B kinase, a critical regulator of mitosis, plays a pivotal role in ensuring chromosomal integrity and preventing polyploidy.
View Article and Find Full Text PDFCarcinogenesis
September 2025
Department of Gastroenterology, Cancer Hospital Affiliated to Shanxi Medical University/Shanxi Province Cancer Hospital/Shanxi Hospital Affiliated to Cancer Hospital, Chinese Academy of Medical Sciences, Taiyuan, China.
Aurora kinase A (AURKA) is a serine/threonine kinase that plays a critical role in cell cycle regulation, particularly during mitosis. Recent studies have identified AURKA as an oncogene overexpressed in various cancers, including gastric cancer (GC). This review summarizes the molecular mechanisms by which AURKA contributes to GC pathogenesis, including its roles in cell proliferation, apoptosis inhibition, epithelial-mesenchymal transition (EMT), and cancer stemness.
View Article and Find Full Text PDFElife
September 2025
State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, China.
Innate immune cells can acquire a memory phenotype, termed trained immunity, but the mechanism underlying the regulation of trained immunity remains largely elusive. Here, we demonstrate that inhibition of Aurora kinase A (AurA) dampens trained immunity induced by β-glucan. ATAC-seq and RNA-seq analysis reveal that AurA inhibition restricts chromatin accessibility of genes associated with inflammatory pathways such as JAK-STAT, TNF, and NF-κB pathways.
View Article and Find Full Text PDFBlood Vessel Thromb Hemost
August 2025
Hematology, Thrombosis and Hemostasis Research Program, Versiti Blood Research Institute, Wauwatosa, WI.
Unopposed platelet activation can be associated with pathologic thrombosis. An intact growth arrest-specific gene 6 (GAS6)/Mer receptor tyrosine kinase (MERTK) signaling pathway contributes importantly to potentiating platelet activation triggered by molecular agonists ex vivo and thrombus stabilization in vivo. We describe, herein, the inhibition of platelet function and stable thrombus formation conferred by iMer, a naturally occurring MERTK splice variant, that acts as a GAS6 decoy receptor and decreases phosphorylation of MERTK.
View Article and Find Full Text PDFMol Ther Oncol
September 2025
Translational Oncology Division, Oncohealth Institute, IIS - Fundación Jiménez Díaz University Hospital (IIS-FJD, UAM), Madrid, Spain.
Anti-epidermal growth factor receptor (EGFR) therapies are the most recommended first-line treatment for wild-type unresectable metastatic colorectal cancer (CRC) according to the European Society for Medical Oncology guidelines. However, primary resistance renders this treatment ineffective for almost 40% of patients. Our previous work identified Aurora kinase A (AURKA) as a key resistance driver through non-canonical, Hippo-independent Yes-associated protein 1 (YAP1) activation.
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