Abstract

The translation process consists of translation factors and ribosomes. Ribosomal components include ribosomal proteins (RP) and ribosomal RNA. Many RPs are involved in assembling ribosomal particles and or stabilizing important regions of rRNA. Besides their conventional roles, RPs have been reported to exhibit secondary functions that have not yet been fully characterized in other cellular processes such as DNA repair, apoptosis, drug resistance, proliferation, and growth inhibition. Since cancer cells require a large amount of protein, they need ribosomes that work much more efficiently than normal cells. Several tumor suppressors and oncogenic proteins control the progression of cancer cells by regulating ribosome biogenesis and protein synthesis. Interestingly, free RPs also have diverse roles in tumorigenesis or tumor suppression. The physiological link between RPs and cancers has been extensively reviewed and elucidated on several pathways, including their interaction with the p53-MDM2 complex. The first evidence of an association between RPs and cancer came from observing the haploinsufficiency of eS4 in Turner Syndrome and eS19 mutation in Diamond-Blackfan Anemia. In the following years, the roles of different RPs in various cancer types such as colorectal cancer, breast cancer, lung adenocarcinoma, T-cell acute lymphoblastic leukemia, prostate cancer, breast cancer, gastric carcinomas, ovarian cancer, and liver cancer have been the subject of research. Apart from their effects on carcinogenesis, it was also emphasized that RPs could be evaluated as predictive biomarkers for diagnosis, prognosis, and treatment for some cancer types. In addition, some studies have been conducted on the use of these proteins in cancer treatment. Identifying novel extra-ribosomal functions of some RPs has identified these proteins as a new class of oncogenic or tumor suppressor factors. Suppression and stimulation of the expression of these novel oncogenic and tumor suppressor proteins, respectively, are considered could open up new therapeutic strategies in cancer therapy.

Highlights

  • The translation mechanism consists of translation factors and ribosomes

  • Biogenesis of eukaryotic ribosomes occurs within the nucleolus and requires the coordinated assembly of four different ribosomal RNA (rRNA) and approximately 80 ribosomal proteins (RP) (Fatica & Tollervey, 2002)

  • The structure of the ribosome has revealed that many RPs can function as RNA chaperones during assembly of ribosomal particles and/or stabilization of important regions of rRNA (Fatica and Tollervey, 2002)

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Summary

Introduction

The cell is the smallest metabolically functional unit of life. Cells can sense external signals and give tightly regulated responses to them at the transcriptional and translational levels. The eukaryotic ribosome is the cellular translation machinery primarily responsible for protein synthesis from messenger RNAs (mRNA) and consists of four types of ribosomal RNA (rRNA) and 80 ribosomal proteins (RP) Production of this machine, called ribosome biogenesis, is an extraordinarily complex process involving all three RNA polymerases and >150 non-ribosomal factors required for the synthesis, processing, transport and assembly of pre-ribosomes (Fatica and Tollervey, 2002; Tschochner and Hurt, 2003). 47S/45S prerRNA synthesized by RNA Polymerase I (RNA Pol I), 5S rRNA produced by RNA Polymerase III (RNA Pol III), and RP-encoding mRNAs produced by RNA Polymerase II (RNA Pol II) non-ribosomal factors and small nucleolar RNAs (snoRNA) to obtain pre-90S ribosomes within the nucleolus, which undergo multiple modifications and subsequent separation into pre-60S and pre-40S particles During their transport from the nucleolus to the cytoplasm, these anterior ribosomes are detached from most of their non-ribosomal factors and matured into 60S and 40S subunits for protein translation (Fatica and Tollervey, 2002; Tschochner and Hurt, 2003). Various methodological approaches have revealed that RPs in eukaryotes are involved in numerous interactions with translation machinery (Graifer & Karpova, 2015)

Regulation of The Cell Cycle
DNA Repair
Regulation of Apoptosis
Ribosomal Proteins in Cancer
Ribosomal Proteins as a Biomarker in Cancer Diagnosis
Ribosomal Proteins in Cancer Treatment
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