alexa Guarding the 'translation apparatus': defective ribosome biogenesis and the p53 signaling pathway.
Haematology

Haematology

Journal of Bone Research

Author(s): Anirban Chakraborty, Tamayo Uechi, Naoya Kenmochi

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Ribosomes, the molecular factories that carry out protein synthesis, are essential for every living cell. Ribosome biogenesis, the process of ribosome synthesis, is highly complex and energy consuming. Over the last decade, many exciting and novel findings have linked various aspects of ribosome biogenesis to cell growth and cell cycle control. Defects in ribosome biogenesis have also been linked to human diseases. It is now clear that disruption of ribosome biogenesis causes nucleolar stress that triggers a p53 signaling pathway, thus providing cells with a surveillance mechanism for monitoring ribosomal integrity. Although the exact mechanisms of p53 induction in response to nucleolar stress are still unknown, several ribosomal proteins have been identified as key players in this ribosome-p53 signaling pathway. Recent studies of human ribosomal pathologies in a variety of animal models have also highlighted the role of this pathway in the pathophysiology of these diseases. However, it remains to be understood why the effect of ribosomal malfunction is not a universal response in all cell types but is restricted to particular tissues, causing the specific phenotypes seen in ribosomal diseases. A challenge for future studies will be to identify additional players in this signaling pathway and to elucidate the underlying molecular mechanisms that link defective ribosome synthesis to p53.

This article was published in Wiley Interdiscip Rev RNA. and referenced in Journal of Bone Research

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