Cell fate determination by ubiquitin-dependent regulation of translation

Metazoan development depends on the accurate execution of differentiation programs that allow pluripotent stem cells to adopt specific fates. Differentiation requires changes to chromatin architecture and transcriptional networks, yet whether other regulatory events support cell-fate determination is less well understood. Here we identify the ubiquitin ligase CUL3 in complex with its vertebrate-specific substrate adaptor KBTBD8 (CUL3KBTBD8) as an essential regulator of human and Xenopus tropicalis neural crest specification. CUL3KBTBD8 monoubiquitylates NOLC1 and its paralogue TCOF1, the mutation of which underlies the neurocristopathy Treacher Collins syndrome. Ubiquitylation drives formation of a TCOF1–NOLC1 platform that connects RNA polymerase I with ribosome modification enzymes and remodels the translational program of differentiating cells in favour of neural crest specification. We conclude that ubiquitin-dependent regulation of translation is an important feature of cell-fate determination.

• Publication year

  2015

• Venue

  Nature

• Publication date

  2015-07-29

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1038/nature14978PMID 26399832PMCID 4602398
• 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.

• Human diseases of the SSU processome.

  2014cited by this paper
• A Transcriptome-wide Atlas of RNP Composition Reveals Diverse Classes of mRNAs and lncRNAs

  2013cited by this paper
• Mechanisms and function of substrate recruitment by F-box proteins

  2013cited by this paper
• The egg and the nucleus: a battle for supremacy

  2013cited by this paper
• Mysterious Ribosomopathies

  2013cited by this paper
• KLHL3 mutations cause familial hyperkalemic hypertension by impairing ion transport in the distal nephron

  2012cited by this paper
• Ubiquitin-dependent regulation of COPII coat size and function

  2012cited by this paper
• Lack of Cul4b, an E3 Ubiquitin Ligase Component, Leads to Embryonic Lethality and Abnormal Placental Development

  2012cited by this paper
• Exome sequencing identifies recurrent SPOP, FOXA1 and MED12 mutations in prostate cancer

  2012cited by this paper
• NOL11, Implicated in the Pathogenesis of North American Indian Childhood Cirrhosis, Is Required for Pre-rRNA Transcription and Processing

  2012cited by this paper
• Specialized ribosomes: a new frontier in gene regulation and organismal biology

  2012cited by this paper
• SCF ubiquitin ligases in the maintenance of genome stability.

  2012cited by this paper
• The ribosome profiling strategy for monitoring translation in vivo by deep sequencing of ribosome-protected mRNA fragments

  2012cited by this paper
• The F-box protein Ppa is a common regulator of core EMT factors Twist, Snail, Slug, and Sip1

  2011cited by this paper
• Systems-wide proteomic analysis in mammalian cells reveals conserved, functional protein turnover.

  2011cited by this paper
• Ribosome-mediated specificity in Hox mRNA translation and vertebrate tissue patterning.

  2011cited by this paper
• Mutations in genes encoding subunits of RNA polymerases I and III cause Treacher Collins syndrome

  2011cited by this paper
• Mapping gene expression in two Xenopus species: evolutionary constraints and developmental flexibility.

  2011cited by this paper
• Integrating diverse genomic data using gene sets

  2011cited by this paper
• rRNA pseudouridylation defects affect ribosomal ligand binding and translational fidelity from yeast to human cells.

  2011cited by this paper
• Analysis of proteome dynamics in the mouse brain

  2010cited by this paper
• Differential expression analysis for sequence count data

  2010cited by this paper
• Prevention of the neurocristopathy Treacher Collins syndrome through inhibition of p53 function

  2009cited by this paper
• Defining the human deubiquitinating enzyme interaction landscape.

  2009cited by this paper
• Highly efficient neural conversion of human ES and iPS cells by dual inhibition of SMAD signaling

  2009cited by this paper
• FBW7 ubiquitin ligase: a tumour suppressor at the crossroads of cell division, growth and differentiation

  2008cited by this paper
• Prevention of the neurocristopathy Treacher Collins syndrome through inhibition of p53 function

  2008cited by this paper
• Mechanism of ubiquitin-chain formation by the human anaphase-promoting complex.

  2008cited by this paper
• Impaired Control of IRES-Mediated Translation in X-Linked Dyskeratosis Congenita

  2006cited by this paper
• The processivity of multiubiquitination by the APC determines the order of substrate degradation.

  2006cited by this paper
• A dominant-negative form of the E3 ubiquitin ligase Cullin-1 disrupts the correct allocation of cell fate in the neural crest lineage

  2006cited by this paper
• Tcof1/Treacle is required for neural crest cell formation and proliferation deficiencies that cause craniofacial abnormalities

  2006cited by this paper
• Function and regulation of cullin–RING ubiquitin ligases

  2005cited by this paper
• Targeted disruption of p185/Cul7 gene results in abnormal vascular morphogenesis

  2003cited by this paper
• Techniques and probes for the study of Xenopus tropicalis development

  2002cited by this paper
• Deletion of the Cul1 gene in mice causes arrest in early embryogenesis and accumulation of cyclin E.

  1999cited by this paper
• Cullin-3 targets cyclin E for ubiquitination and controls S phase in mammalian cells.

  1999cited by this paper
• Positional cloning of a gene involved in the pathogenesis of Treacher Collins syndrome

  1996cited by this paper

• Comprehensive Profiling of N6-methyladnosine (m6A) Readouts Reveals Novel m6A Readers That Regulate Human Embryonic Stem Cell Differentiation.

  2026cites this paper
• sQTLs and eQTLs for growth in broilers identification and characterization of sQTLs and eQTLs associated with growth traits in yellow-feathered broilers.

  2026cites this paper
• Cullin-3 adaptor SHKBP1 inhibits SQSTM1/p62 oligomerization and Keap1 sequestration.

  2026cites this paper
• Nucleolar beacon for monitoring nucleolar morphology and proteomics in living cells

  2025cites this paper
• The Clinical Prediction Value of the Ubiquitination Model Reflecting the Microenvironment Infiltration and Drug Sensitivity in Breast Cancer

  2025cites this paper
• Integrated quantitative proteomics and phosphoproteomics analysis reveals USP46-POU4F1-HPSE signaling axis in the pathogenesis of Hirschsprung disease

  2025cites this paper
• The joint role of the immune microenvironment and N7-methylguanosine for prognosis prediction and targeted therapy in acute myeloid leukemia

  2025cites this paper
• Quantitative Proteomic Analysis Reveals JMJD6 and DNAJB11 as Endogenous Substrates of E3 Ligase RFFL.

  2025cites this paper
• SPOP/NOLC1/B4GALT1 signaling axis enhances paclitaxel resistance in endometrial cancer by inducing O-dysglycosylation

  2025cites this paper
• The intracellular virus-host interface of henipaviruses

  2025cites this paper
• Unveiling Sec31: The regulator of COPII vesicle-dependent secretion and beyond

  2025cites this paper
• Deciphering TCOF1 mutations in Chinese Treacher Collins syndrome patients: insights into pathogenesis and transcriptional disruption

  2025cites this paper
• Unraveling the role of Cullin3 of E3 ubiquitin ligase in salt stress tolerance via proteomics

  2025cites this paper
• Protein pyrophosphorylation by inositol pyrophosphates - detection, function, and regulation.

  2025cites this paper
• Treacle’s ability to form liquid-like phase condensates is essential for nucleolar fibrillar center assembly, efficient rRNA transcription and processing, and rRNA gene repair

  2025cites this paper
• Inhibition of SQSTM1/p62 oligomerization and Keap1 sequestration by the Cullin-3 adaptor SHKBP1

  2025cites this paper
• NOLC1 was identified as a tumor suppressor gene in thyroid cancer and correlated with prognosis by bioinformatics.

  2024cites this paper
• Dynamic regulation of the oxidative stress response by the E3 ligase TRIP12

  2024cites this paper
• Integrative Computational Framework, Dyscovr, Links Mutated Driver Genes to Expression Dysregulation Across 19 Cancer Types

  2024cites this paper
• FOSL1 is a key regulator of a super-enhancer driving TCOF1 expression in triple-negative breast cancer

  2024cites this paper
• Untangling Zebrafish Genetic Annotation: Addressing Complexities and Nomenclature Issues in Orthologous Evaluation of TCOF1 and NOLC1

  2024cites this paper
• Apoptotic metabolites ameliorate bone aging phenotypes via TCOF1/FLVCR1-mediated mitochondrial homeostasis

  2024cites this paper
• Crosstalk between ubiquitination and translation in neurodevelopmental disorders

  2024cites this paper
• Functional Activity of Isoform 2 of Human eRF1

  2024cites this paper
• A novel intronic TCOF1 pathogenic variant in a Chinese family with Treacher Collins syndrome

  2024cites this paper
• Genome-scale exon perturbation screens uncover exons critical for cell fitness.

  2024cites this paper
• Ribosome Assembly and Repair.

  2024cites this paper
• RIBO-former: leveraging ribosome profiling information to improve the detection of translated open reading frames

  2023cites this paper
• PROTAC-Based Protein Degradation as a Promising Strategy for Targeted Therapy in Sarcomas

  2023cites this paper
• Targeted Degradation of XIAP is Sufficient and Specific to Induce Apoptosis in MYCN-overexpressing High-risk Neuroblastoma

  2023cites this paper
• Insights into the diverse mechanisms and effects of variant CUL3-induced familial hyperkalemic hypertension

  2023cites this paper
• A ubiquitin-based effector-to-inhibitor switch coordinates early brain, craniofacial, and skin development

  2023cites this paper
• TRIM50 Inhibits Gastric Cancer Progression by Regulating the Ubiquitination and Nuclear Translocation of JUP

  2023cites this paper
• TREX reveals proteins that bind to specific RNA regions in living cells

  2023cites this paper
• MCM5 is an oncogene of colon adenocarcinoma and promotes progression through cell cycle control.

  2023cites this paper
• Roles of NOLC1 in cancers and viral infection

  2023cites this paper
• Detecting recurrent passenger mutations in melanoma by targeted UV damage sequencing

  2023cites this paper
• Effect of Genetic Factors, Age and Sex on Levels of Circulating Extracellular Vesicles and Platelets

  2023influential citation
• TNIP1 inhibits selective autophagy via bipartite interaction with LC3/GABARAP and TAX1BP1.

  2023cites this paper
• Ribosome biogenesis factors—from names to functions

  2023cites this paper
• A tissue-specific ubiquitin switch coordinates brain, craniofacial, and skin development

  2022cites this paper
• Nucleolar Protein Treacle Is Important for the Efficient Growth of Mumps Virus

  2022cites this paper
• The Functions and Effects of CUL3-E3 Ligases Mediated Non-degradative Ubiquitination.

  2022cites this paper
• Differentiation of Human Induced Pluripotent Stem Cells into Cortical Neurons to Advance Precision Medicine.

  2022cites this paper
• Insights from analyses of low complexity regions with canonical methods for protein sequence comparison

  2022cites this paper
• Henipaviruses and lyssaviruses target nucleolar treacle protein and regulate ribosomal RNA synthesis

  2022cites this paper
• FGF12 is a novel component of the nucleolar NOLC1/TCOF1 ribosome biogenesis complex

  2022cites this paper
• Heterogeneity and dynamic of EMT through the plasticity of ribosome and mRNA translation.

  2022cites this paper
• Orphan quality control shapes network dynamics and gene expression

  2022cites this paper
• Assembly and function of branched ubiquitin chains.

  2022cites this paper
• TNIP1 inhibits Mitophagy via interaction with FIP200 and TAX1BP1

  2022cites this paper
• The Clinical Prediction Value of the Ubiquitination Model Reflecting the Immune Traits in LUAD

  2022cites this paper
• Co-adaptor driven assembly of a CUL3 E3 ligase complex.

  2022cites this paper
• A unified view of low complexity regions ( LCRs ) across species 1

  2022cites this paper
• Nucleolar and Coiled-Body Phosphoprotein 1 Is Associated With Stemness and Represents a Potential Therapeutic Target in Triple-Negative Breast Cancer

  2022cites this paper
• A unified view of low complexity regions (LCRs) across species

  2022cites this paper
• A unified view of LCRs across species 1

  2022cites this paper
• Thousands of human non-AUG extended proteoforms lack evidence of evolutionary selection among mammals

  2022cites this paper
• The COP9 signalosome: A versatile regulatory hub of Cullin-RING ligases.

  2022cites this paper
• The ribosomal chaperone NACA recruits PHD2 to cotranslationally modify HIF‐α

  2022cites this paper
• A single phenylalanine residue in β-arrestin2 critically regulates its binding to G protein–coupled receptors

  2022cites this paper
• Kapd Is Essential for Specification of the Dopaminergic Neurogenesis in Zebrafish Embryos

  2021cites this paper
• Knockdown of NOLC1 Inhibits PI3K-AKT Pathway to Improve the Poor Prognosis of Esophageal Carcinoma

  2021cites this paper
• LZTR1: A promising adaptor of the CUL3 family

  2021cites this paper
• A high-throughput assay for directly monitoring nucleolar rRNA biogenesis

  2021cites this paper
• METTL18-mediated histidine methylation of RPL3 modulates translation elongation for proteostasis maintenance

  2021cites this paper
• Exploring Evidence of Non-coding RNA Translation With Trips-Viz and GWIPS-Viz Browsers

  2021cites this paper
• The role of Beta-arrestin2 nuclear signalling in neuroplasticity

  2021cites this paper
• TCOF1 upregulation in triple-negative breast cancer promotes stemness and tumour growth and correlates with poor prognosis

  2021cites this paper
• The crucial role of model systems in understanding the complexity of cell signaling in human neurocristopathies.

  2021cites this paper
• Novel CUL3 Variant Causing Familial Hyperkalemic Hypertension Impairs Regulation and Function of Ubiquitin Ligase Activity

  2021cites this paper
• Ribosome changes elicit non-canonical translation for chemosurvival in G0 leukemic cells

  2021cites this paper
• Ribosome diversity

  2021cites this paper
• Linkage-specific deubiquitylation by OTUD5 defines an embryonic pathway intolerant to genomic variation

  2021cites this paper
• Surveillance of nucleolar homeostasis and ribosome maturation by autophagy and the ubiquitin-proteasome system.

  2021cites this paper
• Ubiquitin-dependent remodeling of the actin cytoskeleton drives cell fusion.

  2021cites this paper
• TRPV1 Activation Promotes β-arrestin2 Interaction with the Ribosomal Biogenesis Machinery in the Nucleolus: Implications for p53 Regulation and Neurite Outgrowth

  2021cites this paper
• The Role of TCOF1 Gene in Health and Disease: Beyond Treacher Collins Syndrome

  2021influential citation
• An E3 ligase guide to the galaxy of small-molecule-induced protein degradation.

  2021cites this paper
• Prevention methods for Treacher Collins syndrome: A systematic review.

  2020cites this paper
• Tissue- and development-stage–specific mRNA and heterogeneous CNV signatures of human ribosomal proteins in normal and cancer samples

  2020cites this paper
• EDF1 coordinates cellular responses to ribosome collisions

  2020cites this paper
• Structural basis for dimerization quality control

  2020cites this paper
• Loss-of-function mutations of CUL3, a high confidence gene for psychiatric disorders, lead to aberrant neurodevelopment in human induced pluripotent stem cells.

  2020cites this paper
• Cranial Neural Crest Cells and Their Role in the Pathogenesis of Craniofacial Anomalies and Coronal Craniosynostosis

  2020cites this paper
• A Cellular Mechanism to Detect and Alleviate Reductive Stress.

  2020cites this paper
• Control of craniofacial and brain development by Cullin3-RING ubiquitin ligases: Lessons from human disease genetics.

  2020cites this paper
• Unanchored Ubiquitin Chains, Revisited

  2020cites this paper
• Downregulation of the ubiquitin ligase KBTBD8 prevented epithelial ovarian cancer progression

  2020cites this paper
• FBXO11-Mediated Proteolysis of BAHD1 Relieves PRC2-dependent Transcriptional Repression in Erythropoiesis.

  2020cites this paper
• Deubiquitylases in developmental ubiquitin signaling and congenital diseases

  2020cites this paper
• TREACHER COLLINS SYNDROME AND RELATED DISORDERS

  2020cites this paper
• Fbxo9 functions downstream of Sox10 to determine neuron-glial fate choice in the dorsal root ganglia through Neurog2 destabilization

  2020cites this paper
• Nucleolar stress in Drosophila neuroblasts, a model for human ribosomopathies

  2020cites this paper
• Dual Proteome-scale Networks Reveal Cell-specific Remodeling of the Human Interactome

  2020cites this paper
• DNAJB6, a Key Factor in Neuronal Sensitivity to Amyloidogenesis.

  2020cites this paper
• Structural basis for dimerization quality control

  2020cites this paper
• Nucleolar stress in Drosophila neuroblasts, a model for human ribosomopathies

  2019cites this paper
• Post-translational regulation of planarian regeneration.

  2019cites this paper
• Cortical interlaminar astrocytes across the therian mammal radiation

  2019cites this paper