ArticleCell2018
Targeting Processive Transcription Elongation via SEC Disruption for MYC-Induced Cancer Therapy.
Open access · bronzeAbstract read
In one paragraph
Article in Cell, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 87 papers.
0numbers the graph read from it
0cells of the map it votes in
87citing papers in PubMed
5.3field-weighted citation impact, top 3% 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
87 citing papers in PubMed, 124 citations in OpenAlex.
- SEC Mediates mAdvanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- AFF4 Loss Compromises Osteogenesis of Orofacial Mesenchymal Stem Cells During Alveolar Bone Repair via AMPK-Mediated Mitophagy.Cell proliferation · 2026Article
- Targeting super elongation complex-driven RNA polymerase II elongation reduces plaque vulnerability.Signal transduction and targeted therapy · 2026Article
- Cohesin acts as a transcriptional gatekeeper by restraining pause-release to promote processive elongation.Nature communications · 2026Article
- Targeting CDKs in the RNAPII transcription cycle.Nature reviews. Drug discovery · 2026Review
- Regulation of RNA transcript elongation in metazoans and its relevance to disease.Nature reviews. Molecular cell biology · 2026Review
- Stabilization of AFF1 by PARylation ensures transcriptional restart after DNA damage.Nature chemical biology · 2026Article
- DOT1L provides transcriptional memory through PRC1.1 antagonism.Nature cell biology · 2026Article
- MeCP2 interacts with the super elongation complex to regulate transcription.Science advances · 2025Article
- Kinetic measurement of gene-specific RNA polymerase II transcription elongation rates.Genome research · 2025Article
- Targeting processive transcription for Myc-driven circuitry in medulloblastoma.Neuro-oncology · 2025Article
- KAT6A chimeras form a self-reinforcing epigenetic module with NURF and MLL/COMPASS to sustain AML.Genome biology · 2025Article
- Single-molecule live imaging of subunit interactions and exchange within cellular regulatory complexes.Molecular cell · 2025Article
- BET degraders reveal BRD4 disruption of 7SK and P-TEFb is critical for effective reactivation of latent HIV in CD4+ T-cells.Journal of virology · 2025Article
- Identification of a Nuclear Localization Signal (NLS) in Human Transcription Elongation Factor ELL2.Cell biochemistry and function · 2024Article
- High-throughput optimized prime editing mediated endogenous protein tagging for pooled imaging of protein localization.bioRxiv : the preprint server for biology · 2024Article
- Release of P-TEFb from the Super Elongation Complex promotes HIV-1 latency reversal.PLoS pathogens · 2024Article
- Kinetic pathway of HIV-1 TAR cotranscriptional folding.Nucleic acids research · 2024Article
- Rapid P-TEFb-dependent transcriptional reorganization underpins the glioma adaptive response to radiotherapy.Nature communications · 2024Article
- Transcriptional elongation control of hypoxic response.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
27 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
- Commented on by
Authors and funding
15 authors at 1 institution in 1 country.
Kaiwei LiangSimpson Querrey Center for Epigenetics, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA; Department of Biochemistry and Molecular Genetics, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA.
Edwin R SmithSimpson Querrey Center for Epigenetics, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA; Department of Biochemistry and Molecular Genetics, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA; Robert H. Lurie Comprehensive Cancer Center, Northwestern University Feinberg, School of Medicine, 303 E. Superior Street, Chicago, IL 60611, USA.
Yuki AoiSimpson Querrey Center for Epigenetics, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA; Department of Biochemistry and Molecular Genetics, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA.
Kristen L StoltzSimpson Querrey Center for Epigenetics, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA; Department of Biochemistry and Molecular Genetics, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA; Center for Molecular Innovation and Drug Discovery, Northwestern University, 2145 Sheridan Road, Evanston, IL 60208, USA.
Hiroaki KatagiDepartment of Neurosurgery, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
Ashley R WoodfinSimpson Querrey Center for Epigenetics, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA; Department of Biochemistry and Molecular Genetics, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA.
Emily J RendlemanSimpson Querrey Center for Epigenetics, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA; Department of Biochemistry and Molecular Genetics, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA.
Stacy A MarshallSimpson Querrey Center for Epigenetics, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA; Department of Biochemistry and Molecular Genetics, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA.
David C MurraySimpson Querrey Center for Epigenetics, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA; Department of Biochemistry and Molecular Genetics, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA.
Lu WangSimpson Querrey Center for Epigenetics, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA; Department of Biochemistry and Molecular Genetics, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA.
Patrick A OzarkSimpson Querrey Center for Epigenetics, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA; Department of Biochemistry and Molecular Genetics, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA.
Rama K MishraCenter for Molecular Innovation and Drug Discovery, Northwestern University, 2145 Sheridan Road, Evanston, IL 60208, USA; Department of Pharmacology, Northwestern University Feinberg School of Medicine, 303 E. Superior Street, Chicago, IL 60611, USA.
Rintaro HashizumeDepartment of Biochemistry and Molecular Genetics, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA; Department of Neurosurgery, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA; Robert H. Lurie Comprehensive Cancer Center, Northwestern University Feinberg, School of Medicine, 303 E. Superior Street, Chicago, IL 60611, USA.
Gary E SchiltzCenter for Molecular Innovation and Drug Discovery, Northwestern University, 2145 Sheridan Road, Evanston, IL 60208, USA; Department of Pharmacology, Northwestern University Feinberg School of Medicine, 303 E. Superior Street, Chicago, IL 60611, USA; Robert H. Lurie Comprehensive Cancer Center, Northwestern University Feinberg, School of Medicine, 303 E. Superior Street, Chicago, IL 60611, USA.
Ali ShilatifardSimpson Querrey Center for Epigenetics, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA; Department of Biochemistry and Molecular Genetics, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA; Robert H. Lurie Comprehensive Cancer Center, Northwestern University Feinberg, School of Medicine, 303 E. Superior Street, Chicago, IL 60611, USA. Electronic address: ash@northwestern.edu.
Northwestern University · US
Funding
Tumor Environment and Metastasis (TEAM) Research ProgramP30CA060553 · NCI · NORTHWESTERN UNIVERSITY AT CHICAGO · PI Daniela E Matei · 1993 to 2026
$153.9MTRAINING PROGRAM IN SIGNAL TRANSDUCTION AND CANCERT32CA070085 · NCI · NORTHWESTERN UNIVERSITY AT CHICAGO · PI LEONIDAS C. PLATANIAS · 1997 to 2026
$5.7MTranscriptional Elongation Control in Development and DiseaseR01CA214035 · NCI · NORTHWESTERN UNIVERSITY AT CHICAGO · PI SHILATIFARD, ALI · 2016 to 2020
$3.0MTargeting Transcriptional Elongation in Pediatric GliomaR01NS126513 · NINDS · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI Rintaro Hashizume · 2022 to 2026
$1.9MTargeting histone demethylase activity for the treatment of pediatric brainstem gliomaR01NS093079 · NINDS · NORTHWESTERN UNIVERSITY AT CHICAGO · PI HASHIZUME, RINTARO · 2015 to 2019
$1.5MHistone Modification and Transcription Elongation in Human CancerR50CA211428 · NCI · NORTHWESTERN UNIVERSITY AT CHICAGO · PI SMITH, EDWIN R · 2016 to 2020
$925kNCI NIH HHS P30 CA060553NCI NIH HHS R01 CA214035NCI NIH HHS R50 CA211428NCI NIH HHS T32 CA070085NINDS NIH HHS R01 NS093079NINDS NIH HHS R01 NS126513
Abstract
The super elongation complex (SEC) is required for robust and productive transcription through release of RNA polymerase II (Pol II) with its P-TEFb module and promoting transcriptional processivity with its ELL2 subunit. Malfunction of SEC contributes to multiple human diseases including cancer. Here, we identify peptidomimetic lead compounds, KL-1 and its structural homolog KL-2, which disrupt the interaction between the SEC scaffolding protein AFF4 and P-TEFb, resulting in impaired release of Pol II from promoter-proximal pause sites and a reduced average rate of processive transcription elongation. SEC is required for induction of heat-shock genes and treating cells with KL-1 and KL-2 attenuates the heat-shock response from Drosophila to human. SEC inhibition downregulates MYC and MYC-dependent transcriptional programs in mammalian cells and delays tumor progression in a mouse xenograft model of MYC-driven cancer, indicating that small-molecule disruptors of SEC could be used for targeted therapy of MYC-induced cancer.
Indexed as
AnimalsAntineoplastic AgentsDrosophilaFemaleHCT116 CellsHeat-Shock ResponseHEK293 CellsHumansMaleMiceMice, Inbred BALB CNeoplasms, ExperimentalPositive Transcriptional Elongation Factor BProtein BindingProto-Oncogene Proteins c-mycRepressor ProteinsAFF4 protein, humanAntineoplastic AgentsPositive Transcriptional Elongation Factor BProto-Oncogene Proteins c-mycRepressor ProteinsRNA Polymerase IISmall Molecule LibrariesTranscriptional Elongation FactorsMYCprocessive elongationpromoter-proximal pausingSECsuper elongation complextranscriptional addiction in cancertranscription elongation
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.