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Huang, W., Lv, X., Liu, C., Zha, Z., Zhang, H., Jiang, Y., et al. (2012) The N-Terminal Phosphodegron Targets TAZ/WWTR1 Protein for SCFβ-Trcp-Dependent Degradation in Response to Phosphatidylinositol 3-Kinase Inhibition. Journal of Biological Chemistry, 287, 26245-26253.
https://doi.org/10.1074/jbc.m112.382036
has been cited by the following article:
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TITLE:
The NORE1A/RASSF5 Tumor Suppressor Forms a Complex with GSK-3β to Regulate β-Catenin
AUTHORS:
M. Lee Schmidt, Howard Donninger, Geoffrey J. Clark
KEYWORDS:
RAS, NORE1A, RASSF5, GSK-3β, Beta Catenin, HIPPO
JOURNAL NAME:
Journal of Biosciences and Medicines,
Vol.12 No.8,
August
8,
2024
ABSTRACT: NORE1A (RASSF5) is a tumor suppressor of the RASSF family that is often down-regulated in human tumors. NORE1A has multiple roles in controlling cellular homeostasis, one of them being regulating levels of β-catenin by binding and modulating the ubiquitin ligase substrate recognition factor β-TrCP. β-catenin is a major executor of the Wnt pathway. The ubiquitin SCF-β-TrCP ligase complex acts on a phospho-degron site in β-catenin that can be phosphorylated by GSK-3β. We now show that in addition to binding β-TrCP, NORE1A also promotes the phosphorylation of the β-catenin phospho-degron by complexing with the kinase GSK-3β. Indeed, NORE1A enhances the formation of a GSK-3β/β-TrCP complex. A structural mutant of NORE1A that retains β-TrCP binding but will no longer interact with GSK-3β inhibits the β-catenin degrading action of NORE1A. The GSK-3β interaction with NORE1A plays an important role in the biology of NORE1A as a GSK-3β inhibitor blocks NORE1A induced senescence. Thus, we identify a new role for the tumor suppressor NORE1A: The regulation of GSK-3β. GSK-3β has many other substrates including multiple transcription factors and co-activators such as p53 and the Hippo component TAZ. The work implies that NORE1A may be able to influence all of them via this new kinase scaffolding interaction.