TIEG1 modulates β-catenin sub-cellular localization and enhances Wnt signaling in bone
| Autor: | Muzaffer Cicek, Kevin S. Pitel, Nalini M. Rajamannan, Molly Nelson Holte, Sarah G. Withers, K. Venuprasad, John R. Hawse, Elizabeth S. Bruinsma, Frank J. Secreto, Malayannan Subramaniam |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Lymphoid Enhancer-Binding Factor 1 Biology Ligands Models Biological Bone and Bones 03 medical and health sciences 0302 clinical medicine Genetics Animals Wnt Signaling Pathway Protein kinase B beta Catenin Cellular localization Cell Nucleus Mice Knockout Osteoblasts Gene regulation Chromatin and Epigenetics Skull Wnt signaling pathway LRP5 Phenotype Cell biology DNA-Binding Proteins Mice Inbred C57BL Protein Transport 030104 developmental biology Gene Expression Regulation 030220 oncology & carcinogenesis Catenin Female Lithium Chloride Nuclear localization sequence Homeostasis Protein Binding Subcellular Fractions Transcription Factors |
| Zdroj: | Nucleic Acids Research |
| ISSN: | 1362-4962 0305-1048 |
| DOI: | 10.1093/nar/gkx118 |
| Popis: | We have previously demonstrated that TGFβ Inducible Early Gene-1 (TIEG1), also known as KLF10, plays important roles in mediating skeletal development and homeostasis in mice. TIEG1 has also been identified in clinical studies as one of a handful of genes whose altered expression levels or allelic variations are associated with decreased bone mass and osteoporosis in humans. Here, we provide evidence for the first time that TIEG1 is involved in regulating the canonical Wnt signaling pathway in bone through multiple mechanisms of action. Decreased Wnt signaling in the absence of TIEG1 expression is shown to be in part due to impaired β-catenin nuclear localization resulting from alterations in the activity of AKT and GSK-3β. We also provide evidence that TIEG1 interacts with, and serves as a transcriptional co-activator for, Lef1 and β-catenin. Changes in Wnt signaling in the setting of altered TIEG1 expression and/or activity may in part explain the observed osteopenic phenotype of TIEG1 KO mice as well as the known links between TIEG1 expression levels/allelic variations and patients with osteoporosis. |
| Databáze: | OpenAIRE |
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