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Nucleolar stress: Molecular mechanisms and related human diseases

Maehama, Tomohiko Nishio, Miki Otani, Junji Mak, Tak Wah Suzuki, Akira 神戸大学

2023.05

概要

Ribosome biogenesis in the nucleolus is an important process that consumes 80% of a cell's intracellular energy supply. Disruption of this process results in nucleolar stress, triggering the activation of molecular systems that respond to this stress to maintain homeostasis. Although nucleolar stress was originally thought to be caused solely by abnormalities of ribosomal RNA (rRNA) and ribosomal proteins (RPs), an accumulating body of more current evidence suggests that many other factors, including the DNA damage response and oncogenic stress, are also involved in nucleolar stress response signaling. Cells reacting to nucleolar stress undergo cell cycle arrest or programmed death, mainly driven by activation of the tumor suppressor p53. This observation has nominated nucleolar stress as a promising target for cancer therapy. However, paradoxically, some RP mutations have also been implicated in cancer initiation and progression, necessitating caution. In this article, we summarize recent findings on the molecular mechanisms of nucleolar stress and the human ribosomal diseases and cancers that arise in its wake.

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How to cite this article: Maehama T, Nishio M, Otani J, Mak

TW, Suzuki A. Nucleolar stress: Molecular mechanisms and

related human diseases. Cancer Sci. 2023;114:2078-2086.

doi:10.1111/cas.15755

13497006, 2023, 5, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/cas.15755 by Kobe University, Wiley Online Library on [08/05/2023]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License

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