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Watcharasit, P., Bijur, G.N., Zmijewski, J.W., Song, L., Zmijewska, A., Chen, X., et al. (2002) Direct, Activating Interaction between Glycogen Synthase Kinase-3β and p53 after DNA Damage. Proceedings of the National Academy of Sciences of the United States of America, 99, 7951-7955.
https://doi.org/10.1073/pnas.122062299

has been cited by the following article:

• 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.