PTEN represses RNA Polymerase I transcription by disrupting the SL1 complex.
paper
Cited
Public
Unavailable
- Authors
- Zhang, Cheng; Comai, Lucio; Johnson, Deborah L
- Year
- 2005
- Journal
- Molecular and cellular biology
- PMID
- 16055704
- DOI
- 10.1128/MCB.25.16.6899-6911.2005
- PMCID
- PMC1190253
PTEN is a tumor suppressor whose function is frequently lost in human cancer. It possesses a lipid phosphatase activity that represses the activation of PI3 kinase/Akt signaling, leading to decreased cell growth, proliferation, and survival. The potential for PTEN to regulate transcription of the large rRNAs by RNA polymerase I (RNA Pol I) was investigated. As increased synthesis of rRNAs is a hallmark of neoplastic transformation, the ability of PTEN to control the transcription of rRNAs might be crucial for its tumor suppressor function. The expression of PTEN in PTEN-deficient cells represses RNA Pol I transcription, while decreasing PTEN expression enhances transcription. PTEN-mediated repression requires its lipid phosphatase activity and is independent of the p53 status of the cell. This event can be uncoupled from PTEN's ability to regulate the cell cycle. RNA Pol I is regulated through PI3 kinase/Akt/mammalian target of rapamycin/S6 kinase, and the expression of constitutively activated S6 kinase is able to abrogate transcription repression by PTEN. No change in the expression of the RNA Pol I transcription components, upstream binding factor or SL1, was observed upon PTEN expression. However, chromatin immunoprecipitation assays demonstrate that PTEN differentially reduces the occupancy of the SL1 subunits on the rRNA gene promoter. Furthermore, PTEN induces dissociation of the SL1 subunits. Together, these results demonstrate that PTEN represses RNA Pol I transcription through a novel mechanism that involves disruption of the SL1 complex.
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External
| Title | Authors | Journal | Year | Link |
|---|---|---|---|---|
| Combined MYC Activation and PTEN Loss Drives Molecular Features of Aggressive Preinvasive Lesions in Mouse Prostate. | Rubenstein M et al. | β | 2026 | β |
| Nucleolar protein DCAF13 promotes non-small cell lung cancer cell proliferation via facilitating rDNA transcription and ribosome biogenesis. | Wang XM et al. | β | 2025 | β |
| The novel RNA polymerase I transcription inhibitor PMR-116 exploits a critical therapeutic vulnerability in a broad-spectrum of high <i>MYC</i> malignancies | Ferreira R et al. | β | 2025 | β |
| Ribosome Biogenesis and Cancer: Insights into NOB1 and PNO1 Mechanisms. | Ragunath M et al. | β | 2024 | β |
| The impact of ribosome biogenesis in cancer: from proliferation to metastasis. | Hwang SP et al. | β | 2024 | β |
| Hypoxia-induced transcriptional stress is mediated by ROS-induced R-loops. | Ma TS et al. | β | 2023 | β |
| RNA polymerase I subunit RPA43 activates rRNA expression and cell proliferation but inhibits cell migration. | Zhang Y et al. | β | 2023 | β |
| The conserved RNA-binding protein Seb1 promotes cotranscriptional ribosomal RNA processing by controlling RNA polymerase I progression. | Duval M et al. | β | 2023 | β |
| The RNA-Binding Function of Ribosomal Proteins and Ribosome Biogenesis Factors in Human Health and Disease. | Catalanotto C et al. | β | 2023 | β |
| Phosphoinositide 3-kinase signalling in the nucleolus. | Morovicz AP et al. | β | 2022 | β |
| Regulation of RNA Polymerase I Stability and Function. | Pitts S et al. | β | 2022 | β |
| Antagonising Chromatin Remodelling Activities in the Regulation of Mammalian Ribosomal Transcription. | Tariq K et al. | β | 2021 | β |
| Non-canonical role of wild-type SEC23B in the cellular stress response pathway. | Yehia L et al. | β | 2021 | β |
| Recent Developments in Small-Molecule Ligands of Medicinal Relevance for Harnessing the Anticancer Potential of G-Quadruplexes. | Savva L et al. | β | 2021 | β |
| Ribosomal RNA Transcription Regulation in Breast Cancer. | Harold CM et al. | β | 2021 | β |
| Ribosome Biogenesis and Cancer: Overview on Ribosomal Proteins. | Pecoraro A et al. | β | 2021 | β |
| Protein kinase CΞΉ promotes UBF1-ECT2 binding on ribosomal DNA to drive rRNA synthesis and transformed growth of non-small-cell lung cancer cells. | Justilien V et al. | β | 2020 | β |
| PTEN hamartoma tumour syndrome: what happens when there is no PTEN germline mutation? | Yehia L et al. | β | 2020 | β |
| Salubrinal in Combination With 4E1RCat Synergistically Impairs Melanoma Development by Disrupting the Protein Synthetic Machinery. | Kardos GR et al. | β | 2020 | β |
| Effective targeting of RNA polymerase I in treatment-resistant prostate cancer. | Low JY et al. | β | 2019 | β |
| How Cancer Exploits Ribosomal RNA Biogenesis: A Journey beyond the Boundaries of rRNA Transcription. | Gaviraghi M et al. | β | 2019 | β |
| Keeping ribosomal DNA intact: a repeating challenge. | Warmerdam DO et al. | β | 2019 | β |
| Nucleolin reorganization and nucleolar stress in Purkinje cells of mutant PCD mice. | BaltanΓ‘s FC et al. | β | 2019 | β |
| PTEN interacts with the transcription machinery on chromatin and regulates RNA polymerase II-mediated transcription. | Steinbach N et al. | β | 2019 | β |
| The Ribosome Biogenesis-Cancer Connection. | Penzo M et al. | β | 2019 | β |
| Translation regulation in skin cancer from a tRNA point of view. | Grafanaki K et al. | β | 2019 | β |
| Non-canonical role of cancer-associated mutant SEC23B in the ribosome biogenesis pathway. | Yehia L et al. | β | 2018 | β |
| Regulation of RNA Polymerase I Transcription in Development, Disease, and Aging. | Sharifi S et al. | β | 2018 | β |
| RNA Polymerase II-Dependent Transcription Initiated by Selectivity Factor 1: A Central Mechanism Used by MLL Fusion Proteins in Leukemic Transformation. | Yokoyama A | β | 2018 | β |
| ING1 regulates rRNA levels by altering nucleolar chromatin structure and mTOR localization. | Rajarajacholan UK et al. | β | 2017 | β |
| New roles for Dicer in the nucleolus and its relevance to cancer. | Roche B et al. | β | 2017 | β |
| PTENΞ² is an alternatively translated isoform of PTEN that regulates rDNA transcription. | Liang H et al. | β | 2017 | β |
| Ribosomal DNA copy number loss and sequence variation in cancer. | Xu B et al. | β | 2017 | β |
| CX-5461 induces autophagy and inhibits tumor growth via mammalian target of rapamycin-related signaling pathways in osteosarcoma. | Li L et al. | β | 2016 | β |
| Maf1, A New PTEN Target Linking RNA and Lipid Metabolism. | Johnson DL et al. | β | 2016 | β |
| The Epigenetic Pathways to Ribosomal DNA Silencing. | Srivastava R et al. | β | 2016 | β |
| The Evolution of the Ribosomal Protein-MDM2-p53 Pathway. | Deisenroth C et al. | β | 2016 | β |
| The histone demethylase JMJD2A/KDM4A links ribosomal RNA transcription to nutrients and growth factors availability. | Salifou K et al. | β | 2016 | β |
| Depletion of the cisplatin targeted HMGB-box factor UBF selectively induces p53-independent apoptotic death in transformed cells. | Hamdane N et al. | β | 2015 | β |
| Targeted cancer therapy with ribosome biogenesis inhibitors: a real possibility? | Brighenti E et al. | β | 2015 | β |
| The nucleolus as a fundamental regulator of the p53 response and a new target for cancer therapy. | Woods SJ et al. | β | 2015 | β |
| Therapeutic interventions to disrupt the protein synthetic machinery in melanoma. | Kardos GR et al. | β | 2015 | β |
| p53 and ribosome biogenesis stress: the essentials. | Golomb L et al. | β | 2014 | β |
| Ribosomal proteins as novel players in tumorigenesis. | de Las Heras-Rubio A et al. | β | 2014 | β |
| Targeting the nucleolus for cancer intervention. | Quin JE et al. | β | 2014 | β |
| Targeting the nucleolus for cancer-specific activation of p53. | Drygin D et al. | β | 2014 | β |
| Basic mechanisms in RNA polymerase I transcription of the ribosomal RNA genes. | Goodfellow SJ et al. | β | 2013 | β |
| Dysregulation of RNA polymerase I transcription during disease. | Hannan KM et al. | β | 2013 | β |
| Elk1 and AP-1 sites in the TBP promoter mediate alcohol-induced deregulation of Pol III-dependent genes. | Zhong Q et al. | β | 2013 | β |
| P19ARF and RasVΒΉΒ² offer opposing regulation of DHX33 translation to dictate tumor cell fate. | Zhang Y et al. | β | 2013 | β |
| The emerging role of RNA polymerase I transcription machinery in human malignancy: a clinical perspective. | Montanaro L et al. | β | 2013 | β |
| Changes in ribosome biogenesis may induce cancer by down-regulating the cell tumor suppressor potential. | Montanaro L et al. | β | 2012 | β |
| LAS1L interacts with the mammalian Rix1 complex to regulate ribosome biogenesis. | Castle CD et al. | β | 2012 | β |
| RNA polymerase I activity is regulated at multiple steps in the transcription cycle: recent insights into factors that influence transcription elongation. | Schneider DA | β | 2012 | β |
| Transient activation of the PI3K-AKT pathway by hepatitis C virus to enhance viral entry. | Liu Z et al. | β | 2012 | β |
| Alcohol induces RNA polymerase III-dependent transcription through c-Jun by co-regulating TATA-binding protein (TBP) and Brf1 expression. | Zhong S et al. | β | 2011 | β |
| Frontier of epilepsy research - mTOR signaling pathway. | Cho CH | β | 2011 | β |
| Nucleolar disruption and cajal body disassembly are nuclear hallmarks of DNA damage-induced neurodegeneration in purkinje cells. | BaltanΓ‘s FC et al. | β | 2011 | β |
| Pten ablation in adult dopaminergic neurons is neuroprotective in Parkinson's disease models. | Domanskyi A et al. | β | 2011 | β |
| Targeting RNA polymerase I with an oral small molecule CX-5461 inhibits ribosomal RNA synthesis and solid tumor growth. | Drygin D et al. | β | 2011 | β |
| The Ribosomal Protein-Mdm2-p53 Pathway and Energy Metabolism: Bridging the Gap between Feast and Famine. | Deisenroth C et al. | β | 2011 | β |
| The transcription elongation factor Spt5 influences transcription by RNA polymerase I positively and negatively. | Anderson SJ et al. | β | 2011 | β |
| A genome-wide scan for common alleles affecting risk for autism. | Anney R et al. | β | 2010 | β |
| Inhibition of U6 snRNA Transcription by PTEN. | Cabarcas S et al. | β | 2010 | β |
| Las1L is a nucleolar protein required for cell proliferation and ribosome biogenesis. | Castle CD et al. | β | 2010 | β |
| Ribosome biogenesis surveillance: probing the ribosomal protein-Mdm2-p53 pathway. | Deisenroth C et al. | β | 2010 | β |
| The RNA polymerase I transcription machinery: an emerging target for the treatment of cancer. | Drygin D et al. | β | 2010 | β |
| Wisely chosen paths--regulation of rRNA synthesis: delivered on 30 June 2010 at the 35th FEBS Congress in Gothenburg, Sweden. | Grummt I | β | 2010 | β |
| Activation of ribosomal RNA transcription by hepatitis C virus involves upstream binding factor phosphorylation via induction of cyclin D1. | Raychaudhuri S et al. | β | 2009 | β |
| Anticancer activity of CX-3543: a direct inhibitor of rRNA biogenesis. | Drygin D et al. | β | 2009 | β |
| Characterization of the rapamycin-sensitive phosphoproteome reveals that Sch9 is a central coordinator of protein synthesis. | Huber A et al. | β | 2009 | β |
| Epidermal growth factor receptor 1 (EGFR1) and its variant EGFRvIII regulate TATA-binding protein expression through distinct pathways. | Fromm JA et al. | β | 2008 | β |
| Facilitated recycling protects human RNA polymerase III from repression by Maf1 in vitro. | Cabart P et al. | β | 2008 | β |
| PTEN represses RNA polymerase III-dependent transcription by targeting the TFIIIB complex. | Woiwode A et al. | β | 2008 | β |
| RNA polymerases I and III, non-coding RNAs and cancer. | White RJ | β | 2008 | β |
| The glycogen synthase kinase (GSK) 3beta represses RNA polymerase I transcription. | Vincent T et al. | β | 2008 | β |
| Coordinate regulation of ribosome biogenesis and function by the ribosomal protein S6 kinase, a key mediator of mTOR function. | Jastrzebski K et al. | β | 2007 | β |
| Feedback regulation of c-Myc by ribosomal protein L11. | Dai MS et al. | β | 2007 | β |
| GO-2D: identifying 2-dimensional cellular-localized functional modules in Gene Ontology. | Zhu J et al. | β | 2007 | β |
| Mammalian Maf1 is a negative regulator of transcription by all three nuclear RNA polymerases. | Johnson SS et al. | β | 2007 | β |
| TBP is differentially regulated by c-Jun N-terminal kinase 1 (JNK1) and JNK2 through Elk-1, controlling c-Jun expression and cell proliferation. | Zhong S et al. | β | 2007 | β |
| Growth factor signaling regulates elongation of RNA polymerase I transcription in mammals via UBF phosphorylation and r-chromatin remodeling. | Stefanovsky V et al. | β | 2006 | β |
| Thinking globally and acting locally with TOR. | Arsham AM et al. | β | 2006 | β |