ArticleDevelopmental cell2020
PRL3-DDX21 Transcriptional Control of Endolysosomal Genes Restricts Melanocyte Stem Cell Differentiation.
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Article in Developmental cell, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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29citing papers in PubMed
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29 citing papers in PubMed, 47 citations in OpenAlex.
- Loss of MITF activity leads to emergent cell states from the melanocyte stem cell lineage.bioRxiv : the preprint server for biology · 2026Article
- Chemical Probe Discovery for DEAD-Box RNA-Binding Protein DDX21 Using Small-Molecule Microarrays.ACS chemical biology · 2025Article
- Mgat4b-mediated selectiveProceedings of the National Academy of Sciences of the United States of America · 2025Article
- The small molecule ML233 is a direct inhibitor of tyrosinase function.Communications biology · 2025Article
- The small molecule ML233 is a direct inhibitor of tyrosinase function.bioRxiv : the preprint server for biology · 2025Article
- SASH1 S519N Variant Links Skin Hyperpigmentation and Premature Hair Graying to Dysfunction of Melanocyte Lineage.The Journal of investigative dermatology · 2025Article
- Melanocyte lineage dynamics in development, growth and disease.Development (Cambridge, England) · 2024Review
- ALDH1A3-acetaldehyde metabolism potentiates transcriptional heterogeneity in melanoma.Cell reports · 2024Article
- Analysis of the Skin and Brain Transcriptome of Normally Pigmented and Pseudo-Albino Southern Flounder (International journal of molecular sciences · 2024Article
- Protein Tyrosine Phosphatase PRL-3: A Key Player in Cancer Signaling.Biomolecules · 2024Review
- Landscape of enhancer disruption and functional screen in melanoma cells.Genome biology · 2023Article
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- Article
- PRL3 as a therapeutic target for novel cancer immunotherapy in multiple cancer types.Theranostics · 2023Review
- Aldh2 is a lineage-specific metabolic gatekeeper in melanocyte stem cells.Development (Cambridge, England) · 2022Article
- Review
- Tfap2b specifies an embryonic melanocyte stem cell that retains adult multifate potential.Cell reports · 2022Article
- DDX21 Interacts with WDR5 to Promote Colorectal Cancer Cell Proliferation by Activating CDK1 Expression.Journal of Cancer · 2022Article
- Knockdown of DEAD-box RNA helicase 52 (DDX52) suppresses the proliferation of melanoma cells in vitro and of nude mouse xenografts by targeting c-Myc.Bioengineered · 2021Article
- The RNA helicase Ddx21 controls Vegfc-driven developmental lymphangiogenesis by balancing endothelial cell ribosome biogenesis and p53 function.Nature cell biology · 2021Article
Corrections and comments
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Authors and funding
19 authors at 8 institutions in 3 countries.
Jeanette A JohanssonMRC Human Genetics Unit, MRC Institute of Genetics and Molecular Medicine, University of Edinburgh, Western General Hospital, Crewe Road South, Edinburgh EH4 2XU, UK; Cancer Research UK Edinburgh Centre, MRC Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh EH4 2XU, UK.
Kerrie L MarieMRC Human Genetics Unit, MRC Institute of Genetics and Molecular Medicine, University of Edinburgh, Western General Hospital, Crewe Road South, Edinburgh EH4 2XU, UK; Cancer Research UK Edinburgh Centre, MRC Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh EH4 2XU, UK; Laboratory of Cancer Biology and Genetics, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Yuting LuMRC Human Genetics Unit, MRC Institute of Genetics and Molecular Medicine, University of Edinburgh, Western General Hospital, Crewe Road South, Edinburgh EH4 2XU, UK; Cancer Research UK Edinburgh Centre, MRC Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh EH4 2XU, UK.
Alessandro BrombinMRC Human Genetics Unit, MRC Institute of Genetics and Molecular Medicine, University of Edinburgh, Western General Hospital, Crewe Road South, Edinburgh EH4 2XU, UK; Cancer Research UK Edinburgh Centre, MRC Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh EH4 2XU, UK.
Cristina SantorielloStem Cell Program and Division of Hematology, Oncology, Boston Children's Hospital and Dana Farber Cancer Institute, Howard Hughes Medical Institute, Harvard Medical School, Harvard Stem Cell Institute, Stem Cell and Regenerative Biology Department, Harvard University, Boston, USA.
Zhiqiang ZengMRC Human Genetics Unit, MRC Institute of Genetics and Molecular Medicine, University of Edinburgh, Western General Hospital, Crewe Road South, Edinburgh EH4 2XU, UK; Cancer Research UK Edinburgh Centre, MRC Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh EH4 2XU, UK.
Judith ZichMRC Human Genetics Unit, MRC Institute of Genetics and Molecular Medicine, University of Edinburgh, Western General Hospital, Crewe Road South, Edinburgh EH4 2XU, UK; Cancer Research UK Edinburgh Centre, MRC Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh EH4 2XU, UK.
Philippe GautierMRC Human Genetics Unit, MRC Institute of Genetics and Molecular Medicine, University of Edinburgh, Western General Hospital, Crewe Road South, Edinburgh EH4 2XU, UK.
Alex von KriegsheimCancer Research UK Edinburgh Centre, MRC Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh EH4 2XU, UK.
Hannah BrunsdonMRC Human Genetics Unit, MRC Institute of Genetics and Molecular Medicine, University of Edinburgh, Western General Hospital, Crewe Road South, Edinburgh EH4 2XU, UK; Cancer Research UK Edinburgh Centre, MRC Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh EH4 2XU, UK.
Ann P WheelerMRC Human Genetics Unit, MRC Institute of Genetics and Molecular Medicine, University of Edinburgh, Western General Hospital, Crewe Road South, Edinburgh EH4 2XU, UK.
Marcel DregerMRC Human Genetics Unit, MRC Institute of Genetics and Molecular Medicine, University of Edinburgh, Western General Hospital, Crewe Road South, Edinburgh EH4 2XU, UK; Cancer Research UK Edinburgh Centre, MRC Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh EH4 2XU, UK.
Douglas R HoustonInstitute of Quantitative Biology, Biochemistry and Biotechnology, Waddington Building, King's Buildings, University of Edinburgh, Edinburgh EH9 3BF, UK.
Christopher M DooleyWellcome Sanger Institute, Hinxton CB10 1SA, UK; Max-Planck-Institute for Developmental Biology, Department ECNV, Max-Planck-Ring 5, 72076 Tübingen, Germany.
Andrew H SimsCancer Research UK Edinburgh Centre, MRC Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh EH4 2XU, UK.
Elisabeth M Busch-NentwichWellcome Sanger Institute, Hinxton CB10 1SA, UK; Cambridge Institute of Therapeutic Immunology & Infectious Disease (CITIID), Jeffrey Cheah Biomedical Centre, University of Cambridge, Puddicombe Way, Cambridge CB2 0AW, UK.
Leonard I ZonStem Cell Program and Division of Hematology, Oncology, Boston Children's Hospital and Dana Farber Cancer Institute, Howard Hughes Medical Institute, Harvard Medical School, Harvard Stem Cell Institute, Stem Cell and Regenerative Biology Department, Harvard University, Boston, USA.
Robert S IllingworthCentre for Regenerative Medicine, Institute for Regeneration and Repair, The University of Edinburgh, Edinburgh BioQuarter, 5 Little France Drive, Edinburgh EH16 4UU, UK. Electronic address: robert.illingworth@ed.ac.uk.
E Elizabeth PattonMRC Human Genetics Unit, MRC Institute of Genetics and Molecular Medicine, University of Edinburgh, Western General Hospital, Crewe Road South, Edinburgh EH4 2XU, UK; Cancer Research UK Edinburgh Centre, MRC Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh EH4 2XU, UK. Electronic address: e.patton@igmm.ed.ac.uk.
University of Edinburgh · GBMRC Institute of Genetics and Molecular Medicine · GBWestern General Hospital · GBBoston Children's Hospital · USEdinburgh Cancer Research · GBHarvard Stem Cell Institute · USUniversity of Cambridge · GBWellcome Sanger Institute · GB
Funding
Transcriptional mechanisms and melanomaP01CA163222 · NCI · MASSACHUSETTS GENERAL HOSPITAL · PI DAVID E FISHER · 2013 to 2026
$25.3MGenetic Epidermiology of MelanomaR01CA083115 · NCI · UNIVERSITY OF PENNSYLVANIA · PI BISHOP, DAVID TIMOTHY, ELDER, DAVID ERIC · 2001 to 2017
$13.0MCancer Biology in the ZebrafishR01CA103846 · NCI · CHILDREN'S HOSPITAL BOSTON · PI ZON, LEONARD IRA · 2003 to 2022
$7.5MMedical Research Council MC_UU_00007/9Medical Research Council MR/K017047/1Medical Research Council MR/S007644/1NCI NIH HHS P01 CA163222NCI NIH HHS R01 CA083115NCI NIH HHS R01 CA103846Wellcome Trust 098051Wellcome Trust 206194Wellcome Trust 208402/Z/17/Z
Abstract
Melanocytes, replenished throughout life by melanocyte stem cells (MSCs), play a critical role in pigmentation and melanoma. Here, we reveal a function for the metastasis-associated phosphatase of regenerating liver 3 (PRL3) in MSC regeneration. We show that PRL3 binds to the RNA helicase DDX21, thereby restricting productive transcription by RNAPII at master transcription factor (MITF)-regulated endolysosomal vesicle genes. In zebrafish, this mechanism controls premature melanoblast expansion and differentiation from MSCs. In melanoma patients, restricted transcription of this endolysosomal vesicle pathway is a hallmark of PRL3-high melanomas. Our work presents the conceptual advance that PRL3-mediated control of transcriptional elongation is a differentiation checkpoint mechanism for activated MSCs and has clinical relevance for the activity of PRL3 in regenerating tissue and cancer.
Indexed as
AnimalsCell DifferentiationDEAD-box RNA HelicasesGene Expression Regulation, DevelopmentalHumansMelanocytesMelanomaMicrophthalmia-Associated Transcription FactorMutationNeoplasm ProteinsProtein Tyrosine PhosphatasesStem CellsZebrafishZebrafish ProteinsDDX21 protein, humanDEAD-box RNA HelicasesMicrophthalmia-Associated Transcription FactorNeoplasm ProteinsProtein Tyrosine PhosphatasesPTP4A3 protein, humanZebrafish ProteinsDDX21melanocyte stem cellmelanomaMITFPRL3PTP4A3regenerationsmall-molecule screentranscription elongationzebrafish
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