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Ribosome-binding protein 1: A multidimensional regulator of cancer progression and a novel target for precision
Ho Huang1,2, Jia Ouyang2
1Peking University Health Science Center, Peking University, Beijing 100044, P.R. China.
Abstract:
Ribosome-binding protein 1 (RRBP1), a core regulator of endoplasmic reticulum-ribosome interactions, serves key roles in the development and progression of various cancer types by coordinating protein synthesis and organelle dynamic interactions. RRBP1 regulates the unfolded protein response by stabilizing glucose-regulated protein 78 and it enhances cancer cell adaptation to endoplasmic reticulum stress and chemotherapy. The stability of RRBP1 is regulated by N6-methyladenosine modification by methyltransferase-like 3 and deubiquitination by ubiquitin-specific processing protease 35. Furthermore, RRBP1 drives cellular anti-apoptosis mechanisms by activating pro-survival pathways such as TGF-β1/SMAD, PI3K/AKT and Notch or binding cyclic RNAs. By contrast, aberrant activation of kinase function and deubiquitination pathways by RRBP1 fusion genes [RRBP1-anaplastic lymphoma kinase, RRBP1-Raf1 proto-oncogene, serine/threonine kinase and RRBP1-ubiquitin specific peptidase 6] exacerbates malignant progression. Furthermore, the pleiotropic regulation of RRBP1 in neurodegeneration, cardiovascular homeostasis and bone metabolism highlights its environment-dependent functions. The present review identified the multidimensional regulatory network of RRBP1 in cancer and non-cancer systems to enhance the understanding of its molecular mechanism, demonstrated its broad regulatory value and potentially provided a key entry point to analyze the disease and develop precision therapies.
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