beta-Catenin is a central effector of Wnt signaling in embryonic and stem cell development and in tumorigenesis. Here, through a mass spectrometric analysis of a beta-catenin protein complex, we identified 12 proteins as putative beta-catenin interactors. We show that one of them, 14-3-3zeta, enhances beta-catenin-dependent transcription by maintaining a high level of beta-catenin protein in the cytoplasm. More importantly, 14-3-3zeta facilitates activation of beta-catenin by the survival kinase Akt and colocalizes with activated Akt in intestinal stem cells. We propose that Akt phosphorylates beta-catenin, which results in 14-3-3zeta binding and stabilization of beta-catenin, and these interactions may be involved in stem cell development.
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http://dx.doi.org/10.1073/pnas.0406499101 | DOI Listing |
Nat Immunol
January 2025
Experimental Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
Hematopoietic stem cells must mitigate myriad stressors throughout their lifetime to ensure normal blood cell generation. Here, we uncover unfolded protein response stress sensor inositol-requiring enzyme-1α (IRE1α) signaling in hematopoietic stem and progenitor cells (HSPCs) as a safeguard against myeloid leukemogenesis. Activated in part by an NADPH oxidase-2 mechanism, IRE1α-induced X-box binding protein-1 (XBP1) mediated repression of pro-leukemogenic programs exemplified by the Wnt-β-catenin pathway.
View Article and Find Full Text PDFeNeuro
January 2025
Department of Neurology, Quanzhou First Hospital Affiliated to Fujian Medical University, Quanzhou 362002, China.
Acute ischemic stroke (AIS) is a dangerous neurological disease associated with an imbalance in Th17/Treg cells and abnormal activation of the Wnt/β-catenin signaling pathway. This study aims to investigate whether inhibition of miR-155 can activate the Wnt/β-catenin signaling pathway to improve Th17/Treg imbalance and provide neuroprotective effects against stroke. We employed a multi-level experimental design.
View Article and Find Full Text PDFJ Nutr Biochem
January 2025
United States Department of Agriculture, Agricultural Research Service, Grand Forks Human Nutrition Research Center, Grand Forks, North Dakota 58203.
The beneficial effects of dietary fiber for colon health may be due to short chain fatty acids (SCFAs), such as butyrate, produced by colonic bacterial fermentation. In contrast, obesogenic diet induced obesity is linked to increased colon cancer incidence. We hypothesize that increasing fiber intake promotes healthy microbiome and reduces bacterial dysbiosis and oncogenic signaling in the colon of mice fed an obesogenic diet.
View Article and Find Full Text PDFJ Transl Med
January 2025
The Comprehensive Breast Care Center, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710004, China.
Background: Bone marrow mesenchymal stem cells (BMSCs) are a crucial component of the tumor microenvironment (TME), with hypoxic conditions promoting their migration to tumors. Exosomes play a vital role in cell-to-cell communication within the TME. Hypoxic TME have a great impact on the release, uptake and biofunctions of exosomes.
View Article and Find Full Text PDFJ Clin Endocrinol Metab
January 2025
Department of Pediatrics, Ribeirao Preto Medical School - University of Sao Paulo, Ribeirao Preto, Brazil.
Background: Adrenocortical cancer (ACC) is rare and aggressive, with YAP1 overexpression associated with poor outcomes in pediatric patients. In this study, we investigated the mechanisms by which YAP1 drives ACC progression and explored it as a potential target therapy.
Methods: YAP1 expression and methylation in ACC were analyzed from pediatric and adult cohorts.
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