The Effects of Deregulated Ribosomal Biogenesis in Cancer
Open Access
- 30 October 2023
- journal article
- review article
- Published by MDPI AG in Biomolecules
- Vol. 13 (11) , 1593
Abstract
Ribosomes are macromolecular ribonucleoprotein complexes assembled from RNA and proteins. Functional ribosomes arise from the nucleolus, require ribosomal RNA processing and the coordinated assembly of ribosomal proteins (RPs), and are frequently hyperactivated to support the requirement for protein synthesis during the self-biosynthetic and metabolic activities of cancer cells. Studies have provided relevant information on targeted anticancer molecules involved in ribosome biogenesis (RiBi), as increased RiBi is characteristic of many types of cancer. The association between unlimited cell proliferation and alterations in specific steps of RiBi has been highlighted as a possible critical driver of tumorigenesis and metastasis. Thus, alterations in numerous regulators and actors involved in RiBi, particularly in cancer, significantly affect the rate and quality of protein synthesis and, ultimately, the transcriptome to generate the associated proteome. Alterations in RiBi in cancer cells activate nucleolar stress response-related pathways that play important roles in cancer-targeted interventions and immunotherapies. In this review, we focus on the association between alterations in RiBi and cancer. Emphasis is placed on RiBi deregulation and its secondary consequences, including changes in protein synthesis, loss of RPs, adaptive transcription and translation, nucleolar stress regulation, metabolic changes, and the impaired ribosome biogenesis checkpoint.Keywords
Funding Information
- National Natural Science Foundation of China (81372878, 81272873, 82072887, 2020JH2/10300143)
- Joint Project for Key Research and Development Programme of Liaoning province (81372878, 81272873, 82072887, 2020JH2/10300143)
This publication has 159 references indexed in Scilit:
- Mutual protection of ribosomal proteins L5 and L11 from degradation is essential for p53 activation upon ribosomal biogenesis stressProceedings of the National Academy of Sciences, 2012
- A unifying model for mTORC1-mediated regulation of mRNA translationNature, 2012
- The translational landscape of mTOR signalling steers cancer initiation and metastasisNature, 2012
- Widespread Shortening of 3′UTRs by Alternative Cleavage and Polyadenylation Activates Oncogenes in Cancer CellsCell, 2009
- Suppression of Myc oncogenic activity by ribosomal protein haploinsufficiencyNature, 2008
- Hedgehog signaling overrides p53-mediated tumor suppression by activating Mdm2Proceedings of the National Academy of Sciences, 2008
- Inhibition of nucleolar transcription as a trigger for neuronal apoptosisJournal of Neurochemistry, 2008
- Prevention of the neurocristopathy Treacher Collins syndrome through inhibition of p53 functionNature Medicine, 2008
- Pol I Transcription and Pre-rRNA Processing Are Coordinated in a Transcription-dependent Manner in Mammalian CellsMolecular Biology of the Cell, 2007
- Ribosome biogenesis and cell growth: mTOR coordinates transcription by all three classes of nuclear RNA polymerasesOncogene, 2006