Ribosomal proteins as novel players in tumorigenesis

Abstract

Ribosome biogenesis is the most demanding energetic and metabolic expenditure of the cell. The nucleolus, a nuclear compartment, coordinates rRNA transcription, maturation, and assembly into ribosome subunits. The transcription process is highly coordinated with ribosome biogenesis. In this context, ribosomal proteins (RPs) play a crucial role. In the last decade, an increasing number of studies have associated RPs with extraribosomal functions related to proliferation. Importantly, the expression of RPs appears to be deregulated in several human disorders due, at least in part, to genetic mutations. Although the deregulation of RPs in human malignancies is commonly observed, a more complex mechanism is believed to be involved, favoring the tumorigenic process, its progression and metastasis. This review explores the roles of the most frequently mutated oncogenes and tumor suppressor genes in human cancer that modulate ribosome biogenesis, including their interaction with RPs. In this regard, we propose a new focus for novel therapies.

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

“…Furthermore, patients with two human congenital disorders, Diamond-Blackfan anemia (DBA) and 5q-syndrome, both of which are characterized by deletions or mutations in multiple RP genes, are at higher risk of developing cancers. Taken together, these data strongly suggest a close association of dysfunction of RPs with human tumorigenesis (for recent comprehensive reviews, see (de las Heras-Rubio et al, 2014;Kim et al, 2014;Wang et al, 2015a;Zhou et al, 2012)). In this review, we will focus on the roles of RPs in regulation of cell growth, tumorigenesis and genome integrity, and discuss RPs as potential cancer biomarkers for early diagnosis and prognosis.…”

“…During pre-rRNA transcription and processing, many RPs, such as S15, S19, S24, assemble onto the mature rRNA regions of pre-RNA and are involved at various stages of rRNA processing Flygare et al, 2007;Idol et al, 2007;Rouquette et al, 2005). In addition, some RPs, such as L22, L24, and L29, are involved in the interaction between the small and large subunits and the stabilization of the ribosome by surrounding the polypeptide exit channel, whereas other RPs, such as S7, S9, S12, S13, L1, and L5, are responsible for direct contact with tRNAs (de las Heras-Rubio et al, 2014;Wilson and Doudna Cate, 2012). Thus, RPs play significant roles during the assembly of ribosome particles and the regulation of ribosome biogenesis.…”

“…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).…”

Ribosomal Protein L23 Negatively Regulates Cellular Apoptosis via the RPL23/Miz-1/C-Myc Circuit in Higher-Risk Myelodysplastic Syndrome

“…These opposing biological characteristics of BM haematopoietic cells lead to differences in disease progression and prognosis. However, the molecular pathogenesis underlying the apoptotic resistance observed in the BM haematopoietic cells of higher-risk MDS patients is poorly understood.Ribosomal proteins (RPs), which are components of ribosomal subunits, are ubiquitous RNA-binding proteins that carry out multiple auxiliary extraribosomal functions and are moderately related to tumourigenesis [5][6][7] . Ribosomal protein L23 (RPL23) is a protein component of the 60S large ribosomal subunit.…”

“…Ribosomal proteins (RPs), which are components of ribosomal subunits, are ubiquitous RNA-binding proteins that carry out multiple auxiliary extraribosomal functions and are moderately related to tumourigenesis [5][6][7] . Ribosomal protein L23 (RPL23) is a protein component of the 60S large ribosomal subunit.…”