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Liu, S., Fang, X., Hall, H., Yu, S., Smith, D., Lu, Z., et al. (2008) Homozygous Deletion of Glycogen Synthase Kinase 3β Bypasses Senescence Allowing Ras Transformation of Primary Murine Fibroblasts. Proceedings of the National Academy of Sciences of the United States of America, 105, 5248-5253.
https://doi.org/10.1073/pnas.0704242105

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.