Ribosomal Proteins Control Tumor Suppressor Pathways in Response to Nucleolar Stress

Ribosome biogenesis includes the making and processing of ribosomal RNAs, the biosynthesis of ribosomal proteins from their mRNAs in the cytosol and their transport to the nucleolus to assemble pre-ribosomal particles. Several stresses including cellular senescence reduce nucleolar rRNA synthesis and maturation increasing the availability of ribosome-free ribosomal proteins. Several ribosomal proteins can activate the p53 tumor suppressor pathway but cells without p53 can still arrest their proliferation in response to an imbalance between ribosomal proteins and mature rRNA production. Recent results on senescence-associated ribogenesis defects (SARD) show that the ribosomal protein S14 (RPS14 or uS11) can act as a CDK4/6 inhibitor linking ribosome biogenesis defects to the main engine of cell cycle progression. This work offers new insights into the regulation of the cell cycle and suggests novel avenues to design anticancer drugs.

• Publication year

  2019

• Venue

  Bioessays

• Publication date

  2019-02-01

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1002/bies.201800183PMID 30706966
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• Interplay between SUMOylation and NEDDylation regulates RPL11 localization and function

  2018cited by this paper
• Senescence-associated ribosome biogenesis defects contributes to cell cycle arrest through the Rb pathway

  2018cited by this paper
• The Amaryllidaceae Alkaloid Haemanthamine Binds the Eukaryotic Ribosome to Repress Cancer Cell Growth.

  2018cited by this paper
• New tricks from old dogs join the fight against ageing

  2017cited by this paper
• Deletion of ribosomal protein genes is a common vulnerability in human cancer, especially in concert with TP53 mutations

  2017cited by this paper
• Rps26 directs mRNA-specific translation by recognition of Kozak sequence elements

  2017cited by this paper
• Eukaryotic ribosome assembly, transport and quality control

  2017cited by this paper
• Cancer-mutated ribosome protein L22 (RPL22/eL22) suppresses cancer cell survival by blocking p53-MDM2 circuit

  2017cited by this paper
• Inhibition of Pol I transcription treats murine and human AML by targeting the leukemia-initiating cell population.

  2017cited by this paper
• A subset of platinum-containing chemotherapeutic agents kills cells by inducing ribosome biogenesis stress

  2017cited by this paper
• Heterogeneous Ribosomes Preferentially Translate Distinct Subpools of mRNAs Genome-wide.

  2017cited by this paper
• The T-cell leukemia associated ribosomal RPL10 R98S mutation enhances JAK-STAT signaling

  2017cited by this paper
• The ribosomal protein gene RPL5 is a haploinsufficient tumor suppressor in multiple cancer types

  2017cited by this paper
• A tRNA-derived small RNA regulates ribosome biogenesis

  2017cited by this paper
• A redox mechanism underlying nucleolar stress sensing by nucleophosmin

  2016cited by this paper
• The human box C/D snoRNAs U3 and U8 are required for pre-rRNA processing and tumorigenesis

  2016cited by this paper
• Development of Soft Tissue Sarcomas in Ribosomal Proteins L5 and S24 Heterozygous Mice

  2016cited by this paper
• Regulatory role of rpL3 in cell response to nucleolar stress induced by Act D in tumor cells lacking functional p53

  2016cited by this paper
• The Dual Inhibition of RNA Pol I Transcription and PIM Kinase as a New Therapeutic Approach to Treat Advanced Prostate Cancer

  2016cited by this paper
• Involvement of human ribosomal proteins in nucleolar structure and p53-dependent nucleolar stress

  2016cited by this paper
• Whole-exome sequencing in relapsing chronic lymphocytic leukemia: clinical impact of recurrent RPS15 mutations.

  2016cited by this paper
• rpL3 promotes the apoptosis of p53 mutated lung cancer cells by down-regulating CBS and NFκB upon 5-FU treatment

  2016cited by this paper
• GRWD1 negatively regulates p53 via the RPL11–MDM2 pathway and promotes tumorigenesis

  2016cited by this paper
• Structure of human MDM2 complexed with RPL11 reveals the molecular basis of p53 activation

  2015cited by this paper
• Ribosomal proteins: functions beyond the ribosome.

  2015cited by this paper
• Mutations driving CLL and their evolution in progression and relapse

  2015cited by this paper
• Perturbation of ribosome biogenesis drives cells into senescence through 5S RNP-mediated p53 activation.

  2015cited by this paper
• Partial Loss of Rpl11 in Adult Mice Recapitulates Diamond-Blackfan Anemia and Promotes Lymphomagenesis.

  2015cited by this paper
• Targeted cancer therapy with ribosome biogenesis inhibitors: a real possibility?

  2015cited by this paper
• Germline Mutation of RPS20, Encoding a Ribosomal Protein, Causes Predisposition to Hereditary Nonpolyposis Colorectal Carcinoma Without DNA Mismatch Repair Deficiency

  2014cited by this paper
• A new system for naming ribosomal proteins.

  2014cited by this paper
• Discovery and saturation analysis of cancer genes across 21 tumor types

  2014cited by this paper
• Human rpL3 plays a crucial role in cell response to nucleolar stress induced by 5-FU and L-OHP

  2014cited by this paper
• Nucleolar Stress Induces Ubiquitination-independent Proteasomal Degradation of PICT1 Protein*

  2014cited by this paper
• Nuclear PRAS40 couples the Akt/mTORC1 signaling axis to the RPL11-HDM2-p53 nucleolar stress response pathway

  2014cited by this paper
• Bypass of the pre-60S ribosomal quality control as a pathway to oncogenesis

  2014cited by this paper
• Altered translation of GATA1 in Diamond-Blackfan anemia

  2014cited by this paper
• mTOR inhibitors blunt the p53 response to nucleolar stress by regulating RPL11 and MDM2 levels

  2014cited by this paper
• The Tumor Suppressor rpl36 Restrains KRASG12V-Induced Pancreatic Cancer

  2014cited by this paper
• mTORC1 signaling controls multiple steps in ribosome biogenesis.

  2014cited by this paper
• Ribosomal Proteins L5 and L11 Cooperatively Inactivate c-Myc via RNA-induced Silencing Complex

  2013cited by this paper
• Ribosomal Protein S14 Negatively Regulates c-Myc Activity*

  2013cited by this paper
• p53 Acts as a Safeguard of Translational Control by Regulating Fibrillarin and rRNA Methylation in Cancer

  2013cited by this paper
• Ribosomal protein S14 unties the MDM2–p53 loop upon ribosomal stress

  2013cited by this paper
• Tight Coordination of Protein Translation and HSF1 Activation Supports the Anabolic Malignant State

  2013cited by this paper
• 5S ribosomal RNA is an essential component of a nascent ribosomal precursor complex that regulates the Hdm2-p53 checkpoint.

  2013cited by this paper
• Phosphorylation of ribosomal protein S6 attenuates DNA damage and tumor suppression during development of pancreatic cancer.

  2013cited by this paper
• The 5S RNP Couples p53 Homeostasis to Ribosome Biogenesis and Nucleolar Stress

  2013cited by this paper
• Splicing-factor oncoprotein SRSF1 stabilizes p53 via RPL5 and induces cellular senescence.

  2013cited by this paper
• Suprainduction of p53 by disruption of 40S and 60S ribosome biogenesis leads to the activation of a novel G2/M checkpoint.

  2012cited by this paper
• Regulation and function of ribosomal protein S6 kinase (S6K) within mTOR signalling networks.

  2012cited by this paper
• Inactivation of ribosomal protein L22 promotes transformation by induction of the stemness factor, Lin28B.

  2012cited by this paper
• Oncolytic immunotherapy of advanced solid tumors with a CD40L-expressing replicating adenovirus: assessment of safety and immunologic responses in patients.

  2012cited by this paper
• Inhibition of RNA polymerase I as a therapeutic strategy to promote cancer-specific activation of p53.

  2012cited by this paper
• HSF1 drives a transcriptional program distinct from heat shock to support highly malignant human cancers.

  2012cited by this paper
• Exome sequencing identifies mutation in CNOT3 and ribosomal genes RPL5 and RPL10 in T-cell acute lymphoblastic leukemia

  2012cited by this paper
• Incidence of neoplasia in Diamond Blackfan anemia: a report from the Diamond Blackfan Anemia Registry.

  2012cited by this paper
• Mutual protection of ribosomal proteins L5 and L11 from degradation is essential for p53 activation upon ribosomal biogenesis stress

  2012cited by this paper
• Ribosomal protein gene deletions in Diamond-Blackfan anemia.

  2011cited by this paper
• Targeting RNA polymerase I with an oral small molecule CX-5461 inhibits ribosomal RNA synthesis and solid tumor growth.

  2011cited by this paper
• Developmental Arrest of T Cells in Rpl22-Deficient Mice Is Dependent upon Multiple p53 Effectors

  2011cited by this paper
• Interplay between Ribosomal Protein S27a and MDM2 Protein in p53 Activation in Response to Ribosomal Stress*

  2011cited by this paper
• Regulation of the MDM2-P53 pathway and tumor growth by PICT1 via nucleolar RPL11

  2011cited by this paper
• Selective inhibition of rRNA transcription downregulates E2F-1: a new p53-independent mechanism linking cell growth to cell proliferation

  2011cited by this paper
• Haploinsufficiency for ribosomal protein genes causes selective activation of p53 in human erythroid progenitor cells.

  2011cited by this paper
• Control of the senescence-associated secretory phenotype by NF-κB promotes senescence and enhances chemosensitivity.

  2011cited by this paper
• Chemotherapeutic Drugs Inhibit Ribosome Biogenesis at Various Levels*

  2010cited by this paper
• Ribosomal protein genes RPS10 and RPS26 are commonly mutated in Diamond-Blackfan anemia.

  2010cited by this paper
• An ARF-independent c-MYC-activated tumor suppression pathway mediated by ribosomal protein-Mdm2 Interaction.

  2010cited by this paper
• The ARF tumor suppressor controls ribosome biogenesis by regulating the RNA polymerase I transcription factor TTF-I.

  2010cited by this paper
• How common are extraribosomal functions of ribosomal proteins?

  2009cited by this paper
• A p53-dependent mechanism underlies macrocytic anemia in a mouse model of human 5q− syndrome

  2009cited by this paper
• Down‐regulation of pescadillo inhibits proliferation and tumorigenicity of breast cancer cells

  2009cited by this paper
• Cell cycle, CDKs and cancer: a changing paradigm

  2009cited by this paper
• Regulation of nucleolar signalling to p53 through NEDDylation of L11

  2009cited by this paper
• A new database for ribosomal protein genes which are mutated in Diamond‐Blackfan Anemia

  2008cited by this paper
• Ribosome biogenesis is sensed at the Start cell cycle checkpoint.

  2007cited by this paper
• Inhibition of c‐Myc activity by ribosomal protein L11

  2007cited by this paper
• Identification of RPS14 as a 5q- syndrome gene by RNA interference screen

  2007cited by this paper
• Impaired ribosome biogenesis in Diamond-Blackfan anemia.

  2007cited by this paper
• 5-Fluorouracil Activation of p53 Involves an MDM2-Ribosomal Protein Interaction*

  2007cited by this paper
• Analysis of Nucleolar Protein Dynamics Reveals the Nuclear Degradation of Ribosomal Proteins

  2007cited by this paper
• Drosophila TIF-IA is required for ribosome synthesis and cell growth and is regulated by the TOR pathway

  2007cited by this paper
• Ribosomal protein S3: a KH domain subunit in NF-kappaB complexes that mediates selective gene regulation.

  2007cited by this paper
• Ribosomal protein S17 gene (RPS17) is mutated in Diamond‐Blackfan anemia

  2007cited by this paper
• c-Myc binds to human ribosomal DNA and stimulates transcription of rRNA genes by RNA polymerase I

  2005cited by this paper
• RNA polymerases I and III, growth control and cancer

  2005cited by this paper
• c-Myc associates with ribosomal DNA and activates RNA polymerase I transcription

  2005cited by this paper
• Epstein–Barr virus-encoded small RNA induces insulin-like growth factor 1 and supports growth of nasopharyngeal carcinoma-derived cell lines

  2005cited by this paper
• Many Ribosomal Protein Genes Are Cancer Genes in Zebrafish

  2004cited by this paper
• Ribosomal Protein L23 Activates p53 by Inhibiting MDM2 Function in Response to Ribosomal Perturbation but Not to Translation Inhibition

  2004cited by this paper
• mTOR-dependent activation of the transcription factor TIF-IA links rRNA synthesis to nutrient availability.

  2004cited by this paper
• Abolition of Cyclin-Dependent Kinase Inhibitor p16Ink4a and p21Cip1/Waf1 Functions Permits Ras-Induced Anchorage-Independent Growth in Telomerase-Immortalized Human Fibroblasts

  2003cited by this paper
• mTOR-Dependent Regulation of Ribosomal Gene Transcription Requires S6K1 and Is Mediated by Phosphorylation of the Carboxy-Terminal Activation Domain of the Nucleolar Transcription Factor UBF†

  2003cited by this paper
• Comparative analysis of ribosomal proteins in complete genomes: an example of reductive evolution at the domain scale.

  2002cited by this paper
• Loss of p16Ink4a with retention of p19Arf predisposes mice to tumorigenesis

  2001cited by this paper
• Rb and p130 regulate RNA polymerase I transcription: Rb disrupts the interaction between UBF and SL-1

  2000cited by this paper
• Differential Roles for Cyclin-Dependent Kinase Inhibitors p21 and p16 in the Mechanisms of Senescence and Differentiation in Human Fibroblasts

  1999cited by this paper
• Murine fibroblasts lacking p21 undergo senescence and are resistant to transformation by oncogenic Ras

  1999cited by this paper
• Regulation of ribosome biogenesis by the rapamycin-sensitive TOR-signaling pathway in Saccharomyces cerevisiae.

  1999cited by this paper

• Nucleolus, Nucleolar Stress and Cardiovascular Diseases

  2026cites this paper
• A novel MAP7D1 mutation causes mitotic defects and RPS14 accumulation in Shwachman−Diamond syndrome patient cells

  2025cites this paper
• Ubc9‐Mediated SUMOylation of RPL3, an Unappreciated Mechanism against Hepatocyte Senescence by Repressing the DHX9‐p16 Axis

  2025cites this paper
• Burkitt's Lymphoma and Early B Cell Transformation as Paradigms of How Epstein-Barr Virus Overcomes Apoptosis and Ferroptosis.

  2025cites this paper
• Increased chromatin accessibility underpins senescence

  2025cites this paper
• Phase separation via protein-protein and protein-RNA networks coordinates ribosome assembly in the nucleolus.

  2025cites this paper
• Nucleolar stress caused by arginine-rich peptides triggers a ribosomopathy and accelerates aging in mice.

  2024cites this paper
• Fusobacterium nucleatum promotes colorectal cancer through neogenesis of tumor stem cells

  2024cites this paper
• Function of plastid translation in plant temperature acclimation: Retrograde signalling or extraribosomal 'moonlighting' functions?

  2024cites this paper
• Potentials of ribosomopathy gene as pharmaceutical targets for cancer treatment

  2023cites this paper
• Thanksgiving to Yeast, the HMGB Proteins History from Yeast to Cancer

  2023cites this paper
• CDK regulators-Cell cycle progression or apoptosis-Scenarios in normal cells and cancerous cells.

  2023cites this paper
• HMG-boxes, ribosomopathies and neurodegenerative disease

  2023cites this paper
• Nucleolar stress caused by arginine-rich peptides triggers a ribosomopathy and accelerates ageing in mice

  2023cites this paper
• RPS14 promotes the development and progression of glioma via p53 signaling pathway.

  2022cites this paper
• Nucleolar stress: Friend or foe in cardiac function?

  2022cites this paper
• Heliangin acts as a covalent ligand of RPS2 that disrupts pre-rRNA metabolic processes in NPM1-mutated acute myeloid leukemia

  2022cites this paper
• Targeting the nucleolus as a therapeutic strategy in human disease.

  2022cites this paper
• Targeting Ribosome Biogenesis in Cancer: Lessons Learned and Way Forward

  2022cites this paper
• RPS9 promotes the progression of NSCLC via activation Stat3 and Erk signaling pathways

  2022cites this paper
• Meis1 supports leukemogenesis through stimulation of ribosomal biogenesis and Myc

  2022cites this paper
• Identification of Key Deregulated RNA-Binding Proteins in Pancreatic Cancer by Meta-Analysis and Prediction of Their Role as Modulators of Oncogenesis

  2021cites this paper
• Genome-Wide Analysis of Ribosomal Protein GhRPS6 and Its Role in Cotton Verticillium Wilt Resistance

  2021cites this paper
• New Insights into CDK Regulators: Novel Opportunities for Cancer Therapy.

  2021cites this paper
• Rps15a Imparts Chemoresistance by Regulating Cd44 Expression and Cell Stemness in Esophageal Squamous Cell Carcinoma

  2021cites this paper
• Quantitative ubiquitylomics reveals the ubiquitination regulation landscape in oral adenoid cystic carcinoma

  2021cites this paper
• Dynamic regulation and requirement for ribosomal RNA transcription during mammalian development

  2021cites this paper
• Investigation of the molecular causes underlying physical abnormalities in Diamond‐Blackfan anemia patients with RPL5 haploinsufficiency

  2021cites this paper
• A proteomic analysis of Bcl-2 regulation of cell cycle arrest: insight into the mechanisms

  2021cites this paper
• Cellular senescence limits translational readthrough

  2021cites this paper
• A new frontier in Fanconi anemia: From DNA repair to ribosome biogenesis.

  2021cites this paper
• MicroRNAs and long non-coding RNAs as novel regulators of ribosome biogenesis

  2020cites this paper
• iTRAQ-based quantitative glutelin proteomic analysis reveals differentially expressed proteins in the physiological metabolism process during endosperm development and their impacts on yield and quality in autotetraploid rice.

  2020cites this paper
• Exploiting codon usage identifies intensity-specific modifiers of Ras/MAPK signaling in vivo

  2020cites this paper
• Construction of a disease‐specific lncRNA‐miRNA‐mRNA regulatory network reveals potential regulatory axes and prognostic biomarkers for hepatocellular carcinoma

  2020cites this paper
• The circuitry between ribosome biogenesis and translation in stem cell function and ageing.

  2020cites this paper
• Colocalization of MID1IP1 and c-Myc is Critically Involved in Liver Cancer Growth via Regulation of Ribosomal Protein L5 and L11 and CNOT2

  2020cites this paper
• uL3 Mediated Nucleolar Stress Pathway as a New Mechanism of Action of Antiproliferative G-quadruplex TBA Derivatives in Colon Cancer Cells

  2020cites this paper
• A novel intensity-specific screen identifies RpS21 as a modifier of low-intensity MAPK signaling

  2019cites this paper
• Exploiting codon usage identifies RpS21 as an in vivo signal strength-dependent Ras/MAPK regulator

  2019cites this paper
• Ectopically expressed pNO40 suppresses ribosomal RNA synthesis by inhibiting UBF-dependent transcription activation.

  2019cites this paper
• Identification of key candidate genes and pathways in multiple myeloma by integrated bioinformatics analysis

  2019cites this paper
• Ribosomal protein RPL22/eL22 regulates the cell cycle by acting as an inhibitor of the CDK4-cyclin D complex

  2019cites this paper