Emerging roles of nucleolar and ribosomal proteins in cancer, development, and aging

Takada, Hitomi; Kurisaki, Akira

doi:10.1007/s00018-015-1984-1

Cited by 49 publications

(47 citation statements)

References 75 publications

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“…24 Recently, several p53-independent pathways that cause cell cycle arrest or apotptosis in response to alterations of ribosome biogenesis have been described. 25,26 Several findings have shown evidence that a variety of DNA damage agents including 5-FU and L-OHP impair ribosomal biogenesis. 16,27 We have recently demonstrated that human rpL3 acts as stress sensing molecule essential in the cell response to ribosomal stress caused by 5-FU and L-OHP in cancer cells lacking active p53.…”

Section: Discussionmentioning

confidence: 99%

Regulatory role of rpL3 in cell response to nucleolar stress induced by Act D in tumor cells lacking functional p53

et al. 2016

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Many chemotherapeutic drugs cause nucleolar stress and p53-independent pathways mediating the nucleolar stress response are emerging. Here, we demonstrate that ribosomal stress induced by Actinomycin D (Act D) is associated to the up-regulation of ribosomal protein L3 (rpL3) and its accumulation as ribosome-free form in lung and colon cancer cell lines devoid of p53. Free rpL3 regulates p21 expression at transcriptional and post-translational levels through a molecular mechanism involving extracellular-signal-regulated kinases1/2 (ERK1/2) and mouse double minute-2 homolog (MDM2). Our data reveal that rpL3 participates to cell response acting as a critical regulator of apoptosis and cell migration. It is noteworthy that silencing of rpL3 abolishes the cytotoxic effects of Act D suggesting that the loss of rpL3 makes chemotherapy drugs ineffective while rpL3 overexpression associates to a strong increase of Act D-mediated inhibition of cell migration. Taking together our results show that the efficacy of Act D chemotherapy depends on rpL3 status revealing new specific targets involved in the molecular pathways activated by Act D in cancers lacking of p53. Hence, the development of treatments aimed at upregulating rpL3 may be beneficial for the treatment of these cancers.

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Section: Discussionmentioning

confidence: 99%

Regulatory role of rpL3 in cell response to nucleolar stress induced by Act D in tumor cells lacking functional p53

et al. 2016

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“…Besides, any dysregulation of the steps can cause an anomalous pattern of protein synthesis, especially a specific programme of proteins associated with cell growth control, thus leading to an increase of susceptibility to tumorigenesis11. In particular, the ribosome assembly involves the association of rRNAs and ribosomal proteins, and ectopic production or activation of ribosomal proteins have been actually observed in several cancer types3031, such as RPS6 in NSCLC and non-Hodgkin lymphoma3233; RPS7, RPS15A and RPS20 in colorectal cancer343536; RPL5 and RPL10 in T-cell acute lymphoblastic leukemia37; and RPS14 in 5q- syndrome38, a subtype of myelodysplastic syndrome (MDS) with a high propensity to acute myeloid leukemia (AML).…”

Section: Discussionmentioning

confidence: 99%

Highly expressed ribosomal protein L34 indicates poor prognosis in osteosarcoma and its knockdown suppresses osteosarcoma proliferation probably through translational control

Luo

Zhao

Fowdur

et al. 2016

Sci Rep

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Osteosarcoma has devastating health implications on children and adolescents. However, due to its low incidence and high tumor heterogeneity, it is hard to achieve any further improvements in therapy and overall survival. Ribosomal protein L34 (RPL34) has been increasingly recognized to promote the proliferation of malignant cells, but its role in osteosarcoma has not been investigated. In this study, real-time quantitative PCR (RT-qPCR) and immunohistochemistry revealed that RPL34 was highly expressed in osteosarcoma tissues when compared to adjacent tissues and normal bone tissues. Survival analysis showed that high expression of RPL34 predicted a poor prognosis for osteosarcoma patients. Knockdown of RPL34 in Saos-2 cells via lentivirus-mediated small interfering RNA (siRNA) significantly inhibited cell proliferation, induced cell apoptosis and G2/M phase arrest. Moreover, screening of transcription factors using University of California Santa Cruz (UCSC) Genome Browser, protein-protein interaction (PPI) network analysis, Gene Ontology (GO) and pathway enrichment analysis revealed that MYC participates in the transcriptional regulation of RPL34, which interacts with the subunits of eukaryotic translation initiation factor 3 (eIF3) and probably involves the translational control of growth-promoting proteins. Our findings suggest that RPL34 plays an important role in the proliferation of osteosarcoma cells.

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“…As suggested by Warner and McIntosh (Warner and McIntosh, 2009), the following criteria must be met to define extraribosomal functions of RPs: (i) interaction with some nonribosomal components of the cell; (ii) the interaction has physiological effects on cellular functions; (iii) the effects occur away from ribosomes; (iv) the effects do not influence protein synthesis. This section will mainly focus on extraribosomal functions of RPs related to a few key cellular processes whose abnormal regulation would lead to tumorigenesis, including apoptosis, cell cycle arrest, cell proliferation, neoplastic transformation, and cell migration and invasion (de las Heras-Rubio et al, 2014;Takada and Kurisaki, 2015;Wang et al, 2015a) (Table 1).…”

Section: The Extraribosomal Functions Of Rpsmentioning

confidence: 99%

The role of ribosomal proteins in the regulation of cell proliferation, tumorigenesis, and genomic integrity

Xiong

Sun

2016

Sci. China Life Sci.

109

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Ribosomal proteins (RPs), the essential components of the ribosome, are a family of RNA-binding proteins, which play prime roles in ribosome biogenesis and protein translation. Recent studies revealed that RPs have additional extra-ribosomal functions, independent of protein biosynthesis, in regulation of diverse cellular processes. Here, we review recent advances in our understanding of how RPs regulate apoptosis, cell cycle arrest, cell proliferation, neoplastic transformation, cell migration and invasion, and tumorigenesis through both MDM2/p53-dependent and p53-independent mechanisms. We also discuss the roles of RPs in the maintenance of genome integrity via modulating DNA damage response and repair. We further discuss mutations or deletions at the somatic or germline levels of some RPs in human cancers as well as in patients of Diamond-Blackfan anemia and 5q-syndrome with high susceptibility to cancer development. Moreover, we discuss the potential clinical application, based upon abnormal levels of RPs, in biomarker development for early diagnosis and/or prognosis of certain human cancers. Finally, we discuss the pressing issues in the field as future perspectives for better understanding the roles of RPs in human cancers to eventually benefit human health. ribosomal protein, tumorigenesis, genomic integrity, ribosomal stress, p53, MDM2 Citation:Xu, X., Xiong, X., and Sun, Y. (2016). The role of ribosomal proteins in the regulation of cell proliferation, tumorigenesis, and genomic integrity. Sci China Life Sci 59, 656 -672.

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Emerging roles of nucleolar and ribosomal proteins in cancer, development, and aging

Cited by 49 publications

References 75 publications

Regulatory role of rpL3 in cell response to nucleolar stress induced by Act D in tumor cells lacking functional p53

Regulatory role of rpL3 in cell response to nucleolar stress induced by Act D in tumor cells lacking functional p53

Highly expressed ribosomal protein L34 indicates poor prognosis in osteosarcoma and its knockdown suppresses osteosarcoma proliferation probably through translational control

The role of ribosomal proteins in the regulation of cell proliferation, tumorigenesis, and genomic integrity

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