ArticleScientific reports2015
AKT and 14-3-3 regulate Notch4 nuclear localization.
Article in Scientific reports, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
22 citing papers in PubMed, 29 citations in OpenAlex.
- AKT1-Mediated NOTCH1 phosphorylation promotes gastric cancer progression via targeted regulation of IRS-1 transcription.Journal of cancer research and clinical oncology · 2024Article
- Versatility of 14-3-3 proteins and their roles in bone and joint-related diseases.Bone research · 2024Review
- Akt is a mediator of artery specification during zebrafish development.Development (Cambridge, England) · 2024Article
- Roles of Notch Signaling in the Tumor Microenvironment.International journal of molecular sciences · 2022Review
- Notch4 mediates vascular remodeling via ERK/JNK/P38 MAPK signaling pathways in hypoxic pulmonary hypertension.Respiratory research · 2022Article
- Sirtuin1 meditated modification of Notch1 intracellular domain regulates nucleolar localization and activation of distinct signaling cascades.Frontiers in cell and developmental biology · 2022Article
- Spatial regulation and generation of diversity in signaling pathways.Journal of biosciences · 2021Review
- MAPK and Notch-Mediated Effects of Meso-Xanthin F199 Compounds on Proliferative Activity and Apoptosis of Human Melanocytes in Three-Dimensional Culture.BioMed research international · 2021Article
- Top Notch Targeting Strategies in Cancer: A Detailed Overview of Recent Insights and Current Perspectives.Cells · 2020Review
- Monitoring protein communities and their responses to therapeutics.Nature reviews. Drug discovery · 2020Review
- Precision medicine for human cancers with Notch signaling dysregulation (Review).International journal of molecular medicine · 2020Review
- Decoding the PTM-switchboard of Notch.Biochimica et biophysica acta. Molecular cell research · 2019Review
- The mitochondrial metabolic function ofFASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2019Article
- Review
- NOTCH3 expression is linked to breast cancer seeding and distant metastasis.Breast cancer research : BCR · 2018Article
- Notch2 and Proteomic Signatures in Mouse Neointimal Lesion Formation.Arteriosclerosis, thrombosis, and vascular biology · 2018Article
- Moving Breast Cancer Therapy up a Notch.Frontiers in oncology · 2018Review
- UVB-induced nuclear translocation of TC-PTP by AKT/14-3-3σ axis inhibits keratinocyte survival and proliferation.Oncotarget · 2017Article
- Keratins regulate colonic epithelial cell differentiation through the Notch1 signalling pathway.Cell death and differentiation · 2017Article
- Therapeutic implications of cellular and molecular biology of cancer stem cells in melanoma.Molecular cancer · 2017Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 4 institutions in 2 countries.
Funding
Abstract
Members of the Notch family of transmembrane receptors, Notch1-4 in mammals, are involved in the regulation of cell fate decisions and cell proliferation in various organisms. The Notch4 isoform, which is specific to mammals, was originally identified as a viral oncogene in mice, Int3, able to initiate mammary tumors. In humans, Notch4 expression appears to be associated with breast cancer stem cells and endocrine resistance. Following ligand binding, the Notch4 receptor undergoes cleavage at the membrane and the Notch4-intracellular domain (ICD), translocates to the nucleus and regulates gene transcription. Little is known on the mechanisms regulating Notch4-ICD and its nuclear localization. Here, we describe the identification of four distinct AKT phosphorylation sites in human Notch4-ICD and demonstrate that AKT binds Notch4-ICD and phosphorylates all four sites in vitro and in vivo. The phosphorylation in cells is regulated by growth factors and is sensitive to phosphatidyl inositol-3 kinase (PI3K) inhibitors. This phosphorylation generates binding sites to the 14-3-3 regulatory proteins, which are involved in the regulation of nucleocytoplasmic shuttling of target proteins, restricting phosphorylated Notch4-ICD to the cytoplasm. Our findings provide a novel mechanism for Notch4-ICD regulation, suggesting a negative regulatory role for the PI3K-AKT pathway in Notch4 nuclear signaling.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.