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We analyzed the G-actin-regulated transcriptome by gene expression analysis using previously characterized actin-binding drugs. We found many known MAL/MRTF-dependent target genes of serum response factor (SRF), as well as additional directly regulated genes. Surprisingly, several putative antiproliferative target genes were identified, including mig6/errfi-1, a negative regulator of the EGFR family. Mig6 induction occurred through actin-MAL-SRF signaling, and MAL was inducibly recruited to and activated a mig6 promoter element. Upregulation of Mig6 by lipid agonists such as LPA and S1P or actin drugs involved MAL and correlated with decreased activation of EGFR, MAPK/Erk, and c-fos. Mig6 depletion restored EGFR signaling and provided a proliferative advantage. Overexpression of MAL exhibited strong antiproliferative effects requiring the domains for SRF binding and transactivation, which supports antagonistic functions of MAL on growth-promoting signals. Our results show the existence of negatively acting transcriptional networks between pro- and antiproliferative signaling pathways toward SRF.
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http://dx.doi.org/10.1016/j.molcel.2009.07.015 | DOI Listing |
JCI Insight
September 2025
Edinburgh Medical School: Biomedical Sciences & Euan MacDonald Centre for M, University of Edinburgh, Edinburgh, United Kingdom.
Spinal muscular atrophy (SMA) is a neuromuscular disease caused by low levels of SMN protein. Several therapeutic approaches boosting SMN are approved for human patients, delivering remarkable improvements in lifespan and symptoms. However, emerging phenotypes, including neurodevelopmental comorbidities, are being reported in some treated SMA patients, indicative of alterations in brain development.
View Article and Find Full Text PDFMed Oncol
September 2025
Venom and Biotherapeutics Molecules Laboratory, Biotechnology Department, Biotechnology Research Center, Pasteur Institute of Iran, Tehran, Iran.
Neuropeptide Y (NPY) and the voltage-gated potassium channel Kv1.3 are closely associated with breast cancer progression and apoptosis regulation, respectively. NPY receptors (NPYRs), which are overexpressed in breast tumors, contribute to tumor growth, migration, and angiogenesis.
View Article and Find Full Text PDFJ Med Chem
September 2025
Hubei Key Laboratory of Natural Medicinal Chemistry and Resource Evaluation, School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
Psoriasis is a chronic inflammatory disease that affects the quality of life of patients. The aromatic hydrocarbon receptor (AHR) plays a pivotal role in maintaining the skin barrier integrity. In this study, we conducted a comprehensive analysis of the structure-activity relationship of Tapinarof analogues.
View Article and Find Full Text PDFCurr Genet
September 2025
Fermentation and Microbial Biotechnology Division, CSIR-Indian Institute of Integrative Medicine, Canal Road, Jammu-Tawi, 180001, India.
Trichoderma species exhibit remarkable versatility in adaptability and in occupying habitats with lifestyles ranging from mycoparasitism and saprotrophy to endophytism. In this study, we present the first high-quality whole-genome assembly and annotation of T. lixii using Illumina HiSeq technology to explore the mechanisms of endophytic lifestyle and plant colonization.
View Article and Find Full Text PDFFASEB J
September 2025
Department of Surgery, McMaster University, Hamilton, Ontario, Canada.
Severe burns are a major global health concern, and are associated with long-term physical and psychological impairments, multi-organ dysfunction, and substantial morbidity and mortality. While burn injuries in adults trigger systemic immuno-metabolic alterations-characterized by white adipose tissue browning, elevated resting energy expenditure, widespread catabolism, and inflammation-these adaptive responses are considerably impaired in older adults, with molecular mechanisms behind these differences remaining largely unclear. As a key regulator of systemic metabolism, investigating the pathological role of adipose tissue (AT) postburn may reveal novel targets that could potentially improve patient outcomes.
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