ArticleMolecular cell2016
Stress from Nucleotide Depletion Activates the Transcriptional Regulator HEXIM1 to Suppress Melanoma.
Open access · bronzeAbstract read
In one paragraph
Article in Molecular cell, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 papers.
0numbers the graph read from it
0cells of the map it votes in
59citing papers in PubMed
4.5field-weighted citation impact, top 5% of its field
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
59 citing papers in PubMed, 101 citations in OpenAlex.
- Vidofludimus Calcium in Patients With Moderate-to-Severe Ulcerative Colitis: A Randomized, Placebo-Controlled, Phase 2 Trial.Clinical and translational gastroenterology · 2025Trial
- Safety, Tolerability and Pharmacokinetics of Vidofludimus calcium (IMU-838) After Single and Multiple Ascending Oral Doses in Healthy Male Subjects.European journal of drug metabolism and pharmacokinetics · 2020Trial
- The Selective Oral Immunomodulator Vidofludimus in Patients with Active Rheumatoid Arthritis: Safety Results from the COMPONENT Study.Drugs in R&D · 2019Trial
- HEXIM1/P-TEFb complex controls RNA polymerase II pause release and immediate early gene induction following neuronal depolarization.The Journal of biological chemistry · 2026Article
- 7SK-enriched exosomes suppress the cancer phenotypes in human lung cancer cells: insights from 2D and microfluidic 3D in vitro models.Scientific reports · 2026Article
- Synthetic lethality between RB-loss and E2F3 inhibition in small cell cancers targeted by pyrimidine synthesis blockade.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Targeting replication stress in neuroblastoma by exploiting the synergistic potential of second generation RRM2 and CHK1 inhibitors.Cell death & disease · 2026Article
- USP44 regulates HEXIM1 stability to inhibit tumorigenesis and metastasis of oral squamous cell carcinoma.Biology direct · 2024Article
- Nucleotide depletion promotes cell fate transitions by inducing DNA replication stress.Developmental cell · 2024Article
- Melanocyte lineage dynamics in development, growth and disease.Development (Cambridge, England) · 2024Review
- Article
- DHODH inhibition enhances the efficacy of immune checkpoint blockade by increasing cancer cell antigen presentation.bioRxiv : the preprint server for biology · 2024Article
- Article
- Landscape of enhancer disruption and functional screen in melanoma cells.Genome biology · 2023Article
- Crosstalk between glucocorticoid and mineralocorticoid receptors boosts glucocorticoid-induced killing of multiple myeloma cells.Cellular and molecular life sciences : CMLS · 2023Article
- Flavopiridol Mitigates the Progression of Monocrotaline-Induced Pulmonary Hypertension in Rats by Targeting Cyclin-Dependent Kinase 9.Cardiovascular drugs and therapy · 2023Article
- P-TEFb: The master regulator of transcription elongation.Molecular cell · 2023Review
- OverexpressionViruses · 2022Article
- RRM2 enhances MYCN-driven neuroblastoma formation and acts as a synergistic target with CHK1 inhibition.Science advances · 2022Article
- Discovery of a large-scale, cell-state-responsive allosteric switch in the 7SK RNA using DANCE-MaP.Molecular cell · 2022Article
Corrections and comments
- Commented on by
Authors and funding
31 authors at 15 institutions in 2 countries.
Justin L TanHoward Hughes Medical Institute, Stem Cell Program and Division of Pediatric Hematology/Oncology, Boston Children's Hospital, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA; Department of Stem Cell and Regenerative Biology, Harvard Stem Cell Institute, Cambridge, MA 02138, USA.
Rachel D FogleyHoward Hughes Medical Institute, Stem Cell Program and Division of Pediatric Hematology/Oncology, Boston Children's Hospital, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA; Department of Stem Cell and Regenerative Biology, Harvard Stem Cell Institute, Cambridge, MA 02138, USA.
Ryan A FlynnCenter for Personal Dynamic Regulomes, Stanford University School of Medicine, Stanford, CA 94305, USA.
Julien AblainHoward Hughes Medical Institute, Stem Cell Program and Division of Pediatric Hematology/Oncology, Boston Children's Hospital, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA; Department of Stem Cell and Regenerative Biology, Harvard Stem Cell Institute, Cambridge, MA 02138, USA.
Song YangHoward Hughes Medical Institute, Stem Cell Program and Division of Pediatric Hematology/Oncology, Boston Children's Hospital, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA; Department of Stem Cell and Regenerative Biology, Harvard Stem Cell Institute, Cambridge, MA 02138, USA.
Violaine Saint-AndréWhitehead Institute for Biomedical Research and Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02142, USA.
Zi Peng FanWhitehead Institute for Biomedical Research and Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02142, USA.
Brian T DoCenter for Personal Dynamic Regulomes, Stanford University School of Medicine, Stanford, CA 94305, USA.
Alvaro C LagaDepartment of Pathology, Brigham & Women's Hospital, Boston, MA 02215, USA.
Koh FujinagaDepartments of Medicine, Microbiology, and Immunology, University of California, San Francisco, San Francisco, CA 94143, USA.
Cristina SantorielloHoward Hughes Medical Institute, Stem Cell Program and Division of Pediatric Hematology/Oncology, Boston Children's Hospital, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA; Department of Stem Cell and Regenerative Biology, Harvard Stem Cell Institute, Cambridge, MA 02138, USA.
Celeste B GreerDepartment of Pharmacology, School of Medicine, Yale University, New Haven, CT 06520, USA.
Yoon Jung KimDepartment of Biological Sciences, The University of Texas at Dallas, Richardson, TX 75080, USA.
John G ClohessyCancer Research Institute, Beth Israel Deaconess Cancer Center, and Department of Medicine and Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115, USA; Preclinical Murine Pharmacogenetics Facility, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115, USA.
Anne BothmerCancer Research Institute, Beth Israel Deaconess Cancer Center, and Department of Medicine and Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115, USA.
Nicole PandellPreclinical Murine Pharmacogenetics Facility, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115, USA.
Serine AvagyanHoward Hughes Medical Institute, Stem Cell Program and Division of Pediatric Hematology/Oncology, Boston Children's Hospital, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA; Department of Stem Cell and Regenerative Biology, Harvard Stem Cell Institute, Cambridge, MA 02138, USA.
John E BrogieDepartment of Biochemistry, University of Iowa, Iowa City, IA 52242, USA.
Ellen van RooijenHoward Hughes Medical Institute, Stem Cell Program and Division of Pediatric Hematology/Oncology, Boston Children's Hospital, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA; Department of Stem Cell and Regenerative Biology, Harvard Stem Cell Institute, Cambridge, MA 02138, USA.
Elliott J HagedornHoward Hughes Medical Institute, Stem Cell Program and Division of Pediatric Hematology/Oncology, Boston Children's Hospital, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA; Department of Stem Cell and Regenerative Biology, Harvard Stem Cell Institute, Cambridge, MA 02138, USA.
Ng Shyh-ChangGenome Institute of Singapore, 60 Biopolis Street, Singapore 138672, Singapore.
Richard M WhiteMemorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York, NY 10065, USA.
David H PriceDepartment of Biochemistry, University of Iowa, Iowa City, IA 52242, USA.
Pier Paolo PandolfiCancer Research Institute, Beth Israel Deaconess Cancer Center, and Department of Medicine and Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115, USA.
B Matija PeterlinDepartments of Medicine, Microbiology, and Immunology, University of California, San Francisco, San Francisco, CA 94143, USA.
Yi ZhouHoward Hughes Medical Institute, Stem Cell Program and Division of Pediatric Hematology/Oncology, Boston Children's Hospital, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA; Department of Stem Cell and Regenerative Biology, Harvard Stem Cell Institute, Cambridge, MA 02138, USA.
Tae Hoon KimDepartment of Biological Sciences, The University of Texas at Dallas, Richardson, TX 75080, USA.
John M AsaraDivision of Signal Transduction, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.
Howard Y ChangCenter for Personal Dynamic Regulomes, Stanford University School of Medicine, Stanford, CA 94305, USA.
Richard A YoungWhitehead Institute for Biomedical Research and Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02142, USA.
Leonard I ZonHoward Hughes Medical Institute, Stem Cell Program and Division of Pediatric Hematology/Oncology, Boston Children's Hospital, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA; Department of Stem Cell and Regenerative Biology, Harvard Stem Cell Institute, Cambridge, MA 02138, USA. Electronic address: zon@enders.tch.harvard.edu.
Beth Israel Deaconess Medical Center · USHoward Hughes Medical Institute · USMassachusetts Institute of Technology · USStanford University · USDana-Farber Cancer Institute · USHarvard Stem Cell Institute · USHarvard University · USThe University of Texas at Dallas · USUniversity of California, San Francisco · USUniversity of Iowa · USBoston Children's Hospital · USBrigham and Women's Hospital · USCornell University · USGenome Institute of Singapore · SGYale University · US
Funding
VectorP30CA006516 · NCI · DANA-FARBER CANCER INSTITUTE · PI A. Heather Eliassen · 1985 to 2026
$330.6MVIRUS PRODUCTION COREP30CA014051 · NCI · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI MATTHEW G. VANDER HEIDEN · 1985 to 2026
$93.9MX-ray Screening and Rapid Structure DeterminationP50GM082250 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI FRANKEL, ALAN D · 2007 to 2018
$48.8MTuberous Sclerosis-Pathway and PathogenesisP01CA120964 · NCI · BRIGHAM AND WOMEN'S HOSPITAL · PI David J. Kwiatkowski · 2007 to 2026
$35.9MCancer Biology in the ZebrafishR01CA103846 · NCI · CHILDREN'S HOSPITAL BOSTON · PI ZON, LEONARD IRA · 2003 to 2022
$7.5MFACTORS INVOLVED IN TRANSCRIPTION BY RNA POLYMERSASE IIR01GM035500 · NIGMS · UNIVERSITY OF IOWA · PI PRICE, DAVID H · 1985 to 2017
$6.5MINSTITUTIONAL NATIONAL RESEARCH SERVICE AWARDT32GM007324 · NIGMS · YALE UNIVERSITY · PI BENNETT, ANTON M · 1987 to 2022
$6.2MEMBRYONIC HEMATOPOIESISR01HL048801 · NHLBI · CHILDREN'S HOSPITAL BOSTON · PI ZON, LEONARD IRA · 1992 to 2016
$5.7MStructural Motifs in RNAR01HG004361 · NHGRI · STANFORD UNIVERSITY · PI CHANG, HOWARD Y · 2007 to 2018
$4.7MLncRNA regulation of environmental responseR01ES023168 · NIEHS · STANFORD UNIVERSITY · PI CHANG, HOWARD Y · 2013 to 2016
$2.2MTAT TransactivationR01AI125104 · NIAID · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI PETERLIN, BORIS MATIJA · 2016 to 2020
$2.0MAnalysis of Higher Order Chromatin Structures in Normal and Cancer EpigenomesR01CA140485 · NCI · YALE UNIVERSITY · PI KIM, TAE HOON · 2010 to 2014
$1.6MHoward Hughes Medical InstituteNCI NIH HHS 2P01CA120964NCI NIH HHS 5P30CA006516NCI NIH HHS P01 CA120964NCI NIH HHS P30 CA006516NCI NIH HHS P30 CA014051NCI NIH HHS R01 CA103846NCI NIH HHS R01CA103846NCI NIH HHS R01 CA140485NCI NIH HHS R01CA140485NHGRI NIH HHS R01-HG004361NHLBI NIH HHS R01 HL048801NIAID NIH HHS R01 AI125104NIAID NIH HHS R21 AI107067NIAID NIH HHS R21AI107067NIEHS NIH HHS R01-ES023168NIGMS NIH HHS P50 GM082250NIGMS NIH HHS R01 GM035500NIGMS NIH HHS T32 GM007324
Abstract
Studying cancer metabolism gives insight into tumorigenic survival mechanisms and susceptibilities. In melanoma, we identify HEXIM1, a transcription elongation regulator, as a melanoma tumor suppressor that responds to nucleotide stress. HEXIM1 expression is low in melanoma. Its overexpression in a zebrafish melanoma model suppresses cancer formation, while its inactivation accelerates tumor onset in vivo. Knockdown of HEXIM1 rescues zebrafish neural crest defects and human melanoma proliferation defects that arise from nucleotide depletion. Under nucleotide stress, HEXIM1 is induced to form an inhibitory complex with P-TEFb, the kinase that initiates transcription elongation, to inhibit elongation at tumorigenic genes. The resulting alteration in gene expression also causes anti-tumorigenic RNAs to bind to and be stabilized by HEXIM1. HEXIM1 plays an important role in inhibiting cancer cell-specific gene transcription while also facilitating anti-cancer gene expression. Our study reveals an important role for HEXIM1 in coupling nucleotide metabolism with transcriptional regulation in melanoma.
Indexed as
AnimalsCell Line, TumorGene Expression Regulation, NeoplasticHumansMelanomaMelanoma, ExperimentalOncogene ProteinsPositive Transcriptional Elongation Factor BPyrimidinesRNA-Binding ProteinsTranscription FactorsTranscription, GeneticTumor Suppressor ProteinsZebrafishZebrafish ProteinsHEXIM1 protein, humanOncogene ProteinsPositive Transcriptional Elongation Factor BPyrimidinesRNA-Binding ProteinsTranscription FactorsTumor Suppressor ProteinsZebrafish Proteins
Identifiers
What OpenQuestion holds
Textmetadata
LicenceTDM
Read underepoch 390
Registered trials
None linked
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.