We recently isolated a Krüppel-like zinc-finger transcription factor 5 (KLF5; also known as BTEB2 and IKLF), which is markedly induced in activated vascular smooth-muscle cells and fibroblasts. Here we describe our analysis of the in vivo function of KLF5 using heterozygous KLF5-knockout mice (Klf5(+/-)). In response to external stress, Klf5(+/-) mice showed diminished levels of arterial-wall thickening, angiogenesis, cardiac hypertrophy and interstitial fibrosis. Also, angiotensin II induced expression of KLF5, which in turn activated platelet-derived growth factor-A (PDGF-A) and transforming growth factor-beta (TGF-beta) expression. In addition, we determined that KLF5 interacted with the retinoic-acid receptor (RAR), that synthetic RAR ligands modulated KLF5 transcriptional activity, and that in vivo administration of RAR ligands affected stress responses in the cardiovascular system in a KLF5-dependent manner. KLF5 thus seems to be a key element linking external stress and cardiovascular remodeling.
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http://dx.doi.org/10.1038/nm738 | DOI Listing |
Nat Commun
December 2024
Laboratory of Retrovirology, The Rockefeller University, New York, NY, 10065, USA.
ZAP is an antiviral protein that binds to and depletes viral RNA, which is often distinguished from vertebrate host RNA by its elevated CpG content. Two ZAP cofactors, TRIM25 and KHNYN, have activities that are poorly understood. Here, we show that functional interactions between ZAP, TRIM25 and KHNYN involve multiple domains of each protein, and that the ability of TRIM25 to multimerize via its RING domain augments ZAP activity and specificity.
View Article and Find Full Text PDFJ Exp Clin Cancer Res
December 2024
Institute for Research On Cancer and Aging of Nice (IRCAN), CNRS UMR 7284, INSERM U1081, University Côte d'Azur, Nice, France.
Background: Multiple Myeloma (MM) is the second most common hematological malignancy, characterized by the accumulation of monoclonal plasmocytes in the bone marrow. Despite advancements with proteasome inhibitors, immunomodulatory agents, and CD38-targeting antibodies, MM remains largely incurable due to resistant clones and frequent relapses. The success of the proteasome inhibitor bortezomib (BTZ) in MM treatment highlights the critical role of the ubiquitin-proteasome system (UPS) in this disease.
View Article and Find Full Text PDFSci Rep
December 2024
Department of Agronomy and Plant Breeding, Sanandaj Branch, Islamic Azad University, Sanandaj, Iran.
Understanding the genetic basis of drought tolerance in safflower (Carthamus tinctorius L.) is essential for developing resilient varieties. In this study, we performed a genome-wide association study (GWAS) using DArTseq markers to identify marker-trait associations (MTAs) linked to drought tolerance across 90 globally diverse safflower genotypes.
View Article and Find Full Text PDFSci Rep
December 2024
Department of Gynaecology, The Affiliated Wuxi People's Hospital of Nanjing Medical University/Wuxi Medical Center, Nanjing Medical University/Wuxi People's Hospital, 299 Qingyang Road, Wuxi, 214023, Jiangsu, China.
Long non-coding RNAs (lncRNAs) have emerged as crucial regulators in cancer progression. We found lncRNA DNM1P35 is elevated in ovarian tumors compared to normal tissues, and demonstrated that lncRNA DNM1P35 promoted cancer cell proliferation, migration and invasion in SK-OV-3 and OVCAR-3 cell lines. Furthermore, lncRNA DNM1P35 also facilitated the epithelial-mesenchymal transition (EMT) of ovarian cancer cells.
View Article and Find Full Text PDFSci Rep
December 2024
Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
Lung cancer ranks as the most prevalent malignant neoplasm worldwide, contributing significantly to cancer-related mortality. Stemness is a well-recognized factor underlying radiotherapy resistance, recurrence and metastasis in non-small-cell lung cancer (NSCLC) patients. Our prior investigations have established the role of IQ motif containing GTPase-activating protein 3 (IQGAP3) in mediating radiotherapy resistance in lung cancer, but its impact on lung cancer stemness remains unexplored.
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