The Notch pathway controls a very broad spectrum of cell fates in metazoans during development, influencing proliferation, differentiation and cell death. Given its central role in normal development and homeostasis, misregulation of Notch signals can lead to various disorders including cancer. How the Notch pathway mediates such pleiotropic and differential effects is of fundamental importance. It is becoming increasingly clear through a number of large-scale genetic and proteomic studies that Notch interacts with a staggeringly large number of other genes and pathways in a context-dependent, complex, and highly regulated network, which determines the ultimate biological outcome. How best to interpret and analyze the continuously increasing wealth of data on Notch interactors remains a challenge. Here we review the current state of genetic and proteomic data related to the Notch interactome.
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Loss of Notch dimerization perturbs intestinal homeostasis by a mechanism involving HDAC activity.
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 PDFSRCAP is involved in porcine reproductive and respiratory syndrome virus activated Notch signaling pathway.
J Virol
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Department of Fundamental Veterinary Medicine, College of Veterinary Medicine, Shandong Agricultural University, Tai'an, Shandong, China.
Article Synopsis
- Porcine reproductive and respiratory syndrome (PRRS) caused by PRRSV leads to significant economic losses in the pork industry, and the non-structural protein 4 (Nsp4) plays a crucial role in the virus's infection process.
- Using label-free quantitative proteomics, researchers identified SRCAP as a key interacting protein that enhances PRRSV infection by activating non-canonical Notch signaling through specific interaction sites on both proteins.
- Blocking the Notch signaling pathway presents a promising strategy for developing new antiviral therapies against PRRSV infection.
Genetic Clustering of Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy Patients of Colorectal Origin: KRAS and Not TP53 Cluster Alterations are Associated with Poor Outcomes.
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