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Nucleolar Signaling Determines Cell Fate: The RP-Mdm2-p53 Axis Fine-Tunes Cellular Homeostasis

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Nuclear Signaling Pathways and Targeting Transcription in Cancer

Part of the book series: Cancer Drug Discovery and Development ((CDD&D))

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Abstract

One of the main functions of the nucleolus is to conduct ribosome biogenesis, which is the most energy-consuming process in growing cells. Not surprisingly, this process is highly regulated during cellular proliferation when energy consumption levels are relatively high. Various stresses such as genotoxic, osmotic and oncogenic stress as well as metabolic fluctuations converge at the nucleolus and impinge on ribosome biogenesis. Depending on the severity of the insult, nucleolar stress signaling can induce cell cycle arrest, apoptosis or metabolic adaptation. Although mechanisms associated with the nucleolar stress response are complex and remain to be fully elucidated, many of the pathways that convert stress signals into a cellular response link the nucleolus to the tumor suppressor and guardian of the genome known as p53. It is now known that the activation of p53 upon nucleolar signaling occurs predominantly through the ribosomal protein (RP)-Mdm2-p53 axis.

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Authors and Affiliations

  1. Department of Radiation Oncology, Lineberger Comprehensive Cancer Center, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27514, USA

    Yong Liu Ph.D. & Yanping Zhang Ph.D.

  2. Laboratory of Biological Cancer Therapy, Xuzhou Medical College, Xuzhou, Jiangsu, China

    Yanping Zhang Ph.D.

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    Rakesh Kumar

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Liu, Y., Zhang, Y. (2014). Nucleolar Signaling Determines Cell Fate: The RP-Mdm2-p53 Axis Fine-Tunes Cellular Homeostasis. In: Kumar, R. (eds) Nuclear Signaling Pathways and Targeting Transcription in Cancer. Cancer Drug Discovery and Development. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4614-8039-6_9

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