The roles of moonlight ribosomal proteins in the development of human cancers

Molavi, Ghader; Samadi, Nasser; Hosseingholi, Elaheh Zadeh

doi:10.1002/jcp.27722

Cited by 37 publications

(27 citation statements)

References 260 publications

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“…In yeast, at least 10 genes were assigned nonribosomal functions including rRNA processing and assembly, transcription regulation, translation, DNA repair, and replication (Lu, Zhu, Xiong, Wang, & Jia, 2015). Similar extra‐ribosomal functions were also detected in mice and human (Briggs & Dinman, 2017; Molavi, Samadi, & Hosseingholi, 2019). To perform these dual functions, the RPGs in question need to be independently regulated to meet not only the need for new ribosomes, but also to fulfill their specialized function.…”

Section: Regulation Of Ribosome Biogenesis a Tug Of War Between Diversupporting

confidence: 63%

Regulation of ribosomal protein genes: An ordered anarchy

et al. 2020

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Ribosomal protein genes are among the most highly expressed genes in most cell types. Their products are generally essential for ribosome synthesis, which is the cornerstone for cell growth and proliferation. Many cellular resources are dedicated to producing ribosomal proteins and thus this process needs to be regulated in ways that carefully balance the supply of nascent ribosomal proteins with the demand for new ribosomes. Ribosomal protein genes have classically been viewed as a uniform interconnected regulon regulated in eukaryotic cells by target of rapamycin and protein kinase A pathway in response to changes in growth conditions and/or cellular status. However, recent literature depicts a more complex picture in which the amount of ribosomal proteins produced varies between genes in response to two overlapping regulatory circuits. The first includes the classical general ribosome‐producing program and the second is a gene‐specific feature responsible for fine‐tuning the amount of ribosomal proteins produced from each individual ribosomal gene. Unlike the general pathway that is mainly controlled at the level of transcription and translation, this specific regulation of ribosomal protein genes is largely achieved through changes in pre‐mRNA splicing efficiency and mRNA stability. By combining general and specific regulation, the cell can coordinate ribosome production, while allowing functional specialization and diversity. Here we review the many ways ribosomal protein genes are regulated, with special focus on the emerging role of posttranscriptional regulatory events in fine‐tuning the expression of ribosomal protein genes and its role in controlling the potential variation in ribosome functions. This article is categorized under: Translation > Ribosome Biogenesis Translation > Ribosome Structure/Function Translation > Translation Regulation

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Section: Regulation Of Ribosome Biogenesis a Tug Of War Between Diversupporting

confidence: 63%

Regulation of ribosomal protein genes: An ordered anarchy

et al. 2020

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“…A large number of extra-ribosomal moonlighting functions of RPs have been described, of which many relate to established oncogenes and tumor suppressors. We refer to other specialized reviews for an extensive overview on this topic [51], and will only focus on the most established extra-ribosomal functions here.…”

Section: Oncogenic Mechanisms In Ribosomopathiesmentioning

confidence: 99%

“…Collectively this suggests that loss of the tumor suppressive functions of RPL5 (uL18) or RPL11 (uL5) via inactivating mutations might predispose DBA patients to cancer development. While this extra-ribosomal function is most established for RPL5 (uL18) and RPL11 (uL5), many other RPs have also been described to regulate TP53 by binding MDM2 [51].…”

Section: Oncogenic Mechanisms In Ribosomopathiesmentioning

confidence: 99%

Cancer Biogenesis in Ribosomopathies

Sulima

Kampen

Keersmaecker

2019

Cells

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Ribosomopathies are congenital diseases with defects in ribosome assembly and are characterized by elevated cancer risks. Additionally, somatic mutations in ribosomal proteins have recently been linked to a variety of cancers. Despite a clear correlation between ribosome defects and cancer, the molecular mechanisms by which these defects promote tumorigenesis are unclear. In this review, we focus on the emerging mechanisms that link ribosomal defects in ribosomopathies to cancer progression. This includes functional “onco-specialization” of mutant ribosomes, extra-ribosomal consequences of mutations in ribosomal proteins and ribosome assembly factors, and effects of ribosomal mutations on cellular stress and metabolism. We integrate some of these recent findings in a single model that can partially explain the paradoxical transition from hypo- to hyperproliferation phenotypes, as observed in ribosomopathies. Finally, we discuss the current and potential strategies, and the associated challenges for therapeutic intervention in ribosome-mutant diseases.

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“…RPL23A is a component of ribosome and mediates the protein synthesis inside cell. Increased level of RPL23A expression has been observed in liver cancer (Molavi et al, 2019). UBC is responsible for ubiquitylation of many proteins inside cell.…”

Section: Discussionmentioning

confidence: 99%

Identification of Blood-based Non-invasive Biomarkers and Therapeutic Agents against Pancreatic Ductal Adenocarcinoma (PDAC): A Network-based Study

Ullah

Sarkar

Akter

2020

Preprint

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Pancreatic Ductal Adenocarcinoma (PDAC) is the most demolishing form of pancreatic cancer with poor prognosis and rising incidence. Difficulties in the early detection and aggressive biological nature of this disease are responsible for most of the therapeutic failures. In this study publicly available microarray expression data of full RNA from peripheral blood of PDAC patient has been utilized via network-based approach in order to identify potential non-invasive biomarkers and drug targets for early diagnosis and treatment of PDAC. Analysis of differentially expressed genes revealed their predominant involvement in translational process, apoptotic process, protein phosphorylation, immune responses, ATP binding, protein binding and signal transduction. Moreover, CREBBP, MAPK14, MAPK1, SMAD3, UBC, MAGOH, HSP90AB1, RPL23A, ACTB and STAT3 were identified as the best proteome signatures, GATA2, FOXC1, PPARG, E2F1, HINFP, USF2, MEF2A, FOXL1, YY1 and NFIC were identified as the best transcriptional regulatory signatures, and hsa-miR-93, hsa-miR-16, hsa-miR-195, hsa-miR-424, hsa-miR-506, hsa-miR-124, hsa-miR-590-3p, hsa-miR-1, hsa-miR-497 and hsa-miR-9 were identified as the best post-transcriptional regulatory signatures in PDAC patient. Analysis of drug-gene interaction revealed Anisomycin, Azactidine, Arsenic trioxide, Bortezomib, Ulixertinib and some other molecules as the probable candidate molecules which may reverse PDAC condition.

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The roles of moonlight ribosomal proteins in the development of human cancers

Cited by 37 publications

References 260 publications

Regulation of ribosomal protein genes: An ordered anarchy

Regulation of ribosomal protein genes: An ordered anarchy

Cancer Biogenesis in Ribosomopathies

Identification of Blood-based Non-invasive Biomarkers and Therapeutic Agents against Pancreatic Ductal Adenocarcinoma (PDAC): A Network-based Study

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