The NOTCH signaling pathway plays important roles in stem cell maintenance, cell-fate determination and differentiation during development. Following ligand binding, the cleaved NOTCH intracellular domain (NICD) interacts directly with the recombinant signal binding protein for immunoglobulin kappa J region (RBPJ) transcription factor and the resulting complex targets gene expression in the nucleus. To date, four human RBPJ isoforms have been described in Entrez Gene, varying in the first 5'coding exons. Using an improved protocol, we were able to further identify all four known and five novel RBPJ transcript variants in human amniotic fluid (AF) cells, a cell type known for its stem cell characteristics. In addition, we used human embryonal carcinoma (EC) NTera2/D1 (NT2) cells and NT2-derived neuron and astrocytes to compare the expression pattern of RBPJ transcripts. Further examination of RBPJ transcripts showed that the novel splice variants contain open reading frames in-frame with the known isoforms, suggesting that they can putatively generate similar function proteins. All known and novel RBPJ transcripts contain the putative nuclear localization signal (NLS), an important component of RBPJ-mediated gene regulation.
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http://dx.doi.org/10.1007/s12015-010-9162-1 | DOI Listing |
Cell Biol Int
December 2024
College of Veterinary Medicine, Jilin University, Changchun, China.
Melatonin (MT), an endogenous hormone secreted by pineal gland, has the sedative, anti-inflammatory and antioxidant functions. However, there are few studies on whether MT affects the proliferation and differentiation of antler chondrocytes. The present study investigated the influences of MT on the proliferation and differentiation of antler chondrocytes, explored its regulation on runt-related transcription factor 2 (RUNX2), NOTCH1 and sonic hedgehog (SHH) signaling, and elucidated their interplays.
View Article and Find Full Text PDFNan Fang Yi Ke Da Xue Xue Bao
December 2024
Graduate School, Anhui University of Chinese Medicine, Hefei 230031, China.
Objectives: To observe the role of miR-139-5p and Notch1 signaling pathway in regulation of homing of bone mesenchymal stem cells (BMSCs) of asthmatic rats.
Methods: Normal rat BMSCs were co-cultured with bronchial epithelial cells from normal or asthmatic rats, followed by transfection with miR-139-5p mimics or a negative control sequence. The changes in cell viability and cell cycle were analyzed, and the cellular expressions of CXCR4 and SDF-1 were detected using immunofluorescence staining.
J Cancer Res Clin Oncol
December 2024
The First Clinical Medical College, Lanzhou University, Lanzhou, 730000, China.
Purpose: This study aimed to investigate that AKT1-Mediated NOTCH1 phosphorylation promotes gastric cancer (GC) progression via targeted regulation of IRS-1 transcription.
Methods: The study utilized databases such as PhosphositePlus, TRANSFAC, CHEA, GPS 5.0, and TCGA, along with experimental techniques including Western Blot, co-IP, in vitro kinase assay, construction of lentiviral overexpression and silencing vectors, immunoprecipitation, modified proteomics, immunofluorescence, ChIP-PCR, EdU assay, Transwell assay, and scratch assay to investigate the effects of AKT1-induced Notch1 phosphorylation on cell proliferation, invasion and migration in vitro, as well as growth and epithelial-mesenchymal transition (EMT) in vivo.
PLoS Genet
December 2024
Division of Developmental Biology, Department of Pediatrics, University of Cincinnati College of Medicine and Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, United States of America.
A tri-protein complex containing NICD, RBPj and MAML1 binds DNA as monomer or as cooperative dimers to regulate transcription. Mice expressing Notch dimerization-deficient alleles (NDD) of Notch1 and Notch2 are sensitized to environmental insults but otherwise develop and age normally. Transcriptomic analysis of colonic spheroids uncovered no evidence of dimer-dependent target gene miss-regulation, confirmed impaired stem cell maintenance in-vitro, and discovered an elevated signature of epithelial innate immune response to symbionts, a likely underlying cause for heightened sensitivity in NDD mice.
View Article and Find Full Text PDFEMBO Mol Med
December 2024
Ecole Polytechnique Fédérale de Lausanne (EPFL), School of Life Sciences, Swiss Institute for Experimental Cancer Research (ISREC), Swiss Cancer Center Leman (SCCL), Station 19, CH-1015, Lausanne, Switzerland.
Cancer cell plasticity contributes significantly to the failure of chemo- and targeted therapies in triple-negative breast cancer (TNBC). Molecular mechanisms of therapy-induced tumor cell plasticity and associated resistance are largely unknown. Using a genome-wide CRISPR-Cas9 screen, we investigated escape mechanisms of NOTCH-driven TNBC treated with a gamma-secretase inhibitor (GSI) and identified SOX2 as a target of resistance to Notch inhibition.
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