Evidence map›Paper›PMID 30581133›Full record

ArticleCell chemical biology2019

Allosteric Inhibition of Ubiquitin-like Modifications by a Class of Inhibitor of SUMO-Activating Enzyme.

Yi-Jia Li, Li Du, Jianghai Wang, Ramir Vega, Terry D Lee, Yunan Miao, Grace Aldana-Masangkay, Eric R Samuels, Baozong Li, S Xiaohu Ouyang and 7 more

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell chemical biology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.

0numbers the graph read from it
0cells of the map it votes in
27citing papers in PubMed
2.4field-weighted citation impact, top 10% of its field
1 · What the graph read from it

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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

27 citing papers in PubMed, 47 citations in OpenAlex.

  1. Article
  2. Article
  3. The role of SUMOylation in epithelial-mesenchymal transition.Journal of molecular medicine (Berlin, Germany) · 2025
    Review
  4. Immune regulation by the SUMO family.Nature reviews. Immunology · 2025
    Review
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

17 authors at 4 institutions in 1 country.

Yi-Jia LiDepartment of Molecular Medicine, The Beckman Research Institute, City of Hope National Medical Center, Duarte, CA, USA.
Li DuDepartment of Molecular Medicine, The Beckman Research Institute, City of Hope National Medical Center, Duarte, CA, USA.
Jianghai WangDepartment of Molecular Medicine, The Beckman Research Institute, City of Hope National Medical Center, Duarte, CA, USA.
Ramir VegaDepartment of Molecular Medicine, The Beckman Research Institute, City of Hope National Medical Center, Duarte, CA, USA.
Terry D LeeDepartment of Immunology, The Beckman Research Institute, City of Hope National Medical Center, Duarte, CA, USA; Irell and Manella Graduate School of Biological Sciences of City of Hope, Duarte, CA, USA.
Yunan MiaoDepartment of Immunology, The Beckman Research Institute, City of Hope National Medical Center, Duarte, CA, USA; Irell and Manella Graduate School of Biological Sciences of City of Hope, Duarte, CA, USA.
Grace Aldana-MasangkayDepartment of Molecular Medicine, The Beckman Research Institute, City of Hope National Medical Center, Duarte, CA, USA.
Eric R SamuelsDepartment of Molecular Medicine, The Beckman Research Institute, City of Hope National Medical Center, Duarte, CA, USA.
Baozong LiDepartment of Molecular Medicine, The Beckman Research Institute, City of Hope National Medical Center, Duarte, CA, USA.
S Xiaohu OuyangSUMO Biosciences, Inc., 2265 E Foothill Boulevard, Pasadena, CA 91107, USA.
Sharon A ColaycoConrad Prebys Center for Chemical Genomics, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA, USA.
Ekaterina V BobkovaConrad Prebys Center for Chemical Genomics, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA, USA.
Daniela B DivlianskaConrad Prebys Center for Chemical Genomics, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA, USA.
Eduard SergienkoConrad Prebys Center for Chemical Genomics, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA, USA.
Thomas D Y ChungConrad Prebys Center for Chemical Genomics, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA, USA.
Marwan FakihDepartment of Medical Oncology, City of Hope National Medical Center, Duarte, CA, USA.
Yuan ChenDepartment of Molecular Medicine, The Beckman Research Institute, City of Hope National Medical Center, Duarte, CA, USA; Irell and Manella Graduate School of Biological Sciences of City of Hope, Duarte, CA, USA. Electronic address: ychen@coh.org.
City Of Hope National Medical Center · USDiscovery Institute · USSanford Burnham Prebys Medical Discovery Institute · USCity of Hope · US

Funding

Transgenic Mouse FacilityP30CA033572 · NCI · CITY OF HOPE/BECKMAN RESEARCH INSTITUTE · PI XIWEI WU · 1985 to 2026
$86.3M
Sanford-Burnham Center for Chemical GenomicsU54HG005033 · NHGRI · SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE · PI JACKSON, MICHAEL · 2008 to 2012
$72.5M
SUMO modification and DNA damage response in cancer therapyR01GM086171 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI CHEN, YUAN · 2008 to 2020
$5.2M
Targeting c-Myc and Proteasome Inhibitor Resistance in Multiple MyelomaR01CA212119 · NCI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI CHEN, YUAN · 2017 to 2021
$2.8M
SUMO Modification and Cancer TherapyR01CA265410 · NCI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI CHEN, YUAN · 2021 to 2025
$2.5M
K-Ras sumoylation in cell proliferation and transformationR01CA216987 · NCI · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI CHEN, YUAN, DAI, WEI · 2017 to 2021
$2.5M
Design of a Covalent Inhibitor for c-Myc-Dependent CancersR44CA189499 · NCI · SUVALENT THERAPEUTICS, INC. · PI OUYANG, SHAWN XIAOHU · 2015 to 2016
$2.0M
NMR Studies of Ku70 and Ku80 DomainsR01CA094595 · NCI · CITY OF HOPE/BECKMAN RESEARCH INSTITUTE · PI CHEN, YUAN · 2001 to 2005
$1.7M
SENP:Conformational Dynamics and Inhibition by Small MoleculesR01GM102538 · NIGMS · BECKMAN RESEARCH INSTITUTE/CITY OF HOPE · PI CHEN, YUAN · 2012 to 2015
$1.7M
A high throughput screening assay for the identification of SUMOylation inhibitorR03DA026556 · NIDA · BECKMAN RESEARCH INSTITUTE/CITY OF HOPE · PI CHEN, YUAN · 2008 to 2008
$25k
NCI NIH HHS P30 CA033572NCI NIH HHS R01 CA094595NCI NIH HHS R01 CA212119NCI NIH HHS R01 CA216987NCI NIH HHS R01 CA265410NCI NIH HHS R44 CA189499NHGRI NIH HHS U54 HG005033NIDA NIH HHS R03 DA026556NIGMS NIH HHS R01 GM086171NIGMS NIH HHS R01 GM102538
6 · The paper itself

Abstract

Ubiquitin-like (Ubl) post-translational modifications are potential targets for therapeutics. However, the only known mechanism for inhibiting a Ubl-activating enzyme is through targeting its ATP-binding site. Here we identify an allosteric inhibitory site in the small ubiquitin-like modifier (SUMO)-activating enzyme (E1). This site was unexpected because both it and analogous sites are deeply buried in all previously solved structures of E1s of ubiquitin-like modifiers (Ubl). The inhibitor not only suppresses SUMO E1 activity, but also enhances its degradation in vivo, presumably due to a conformational change induced by the compound. In addition, the lead compound increased the expression of miR-34b and reduced c-Myc levels in lymphoma and colorectal cancer cell lines and a colorectal cancer xenograft mouse model. Identification of this first-in-class inhibitor of SUMO E1 is a major advance in modulating Ubl modifications for therapeutic aims.

Indexed as

SumoylationAllosteric RegulationAllosteric SiteAnimalsCell Line, TumorHigh-Throughput Screening AssaysHumansMiceMice, SCIDMicroRNAsProto-Oncogene Proteins c-mycSmall Molecule LibrariesTransplantation, HeterologousUbiquitinUbiquitin-Activating EnzymesUbiquitinationMicroRNAsMIRN34 microRNA, humanProto-Oncogene Proteins c-mycSmall Molecule LibrariesUbiquitinUbiquitin-Activating Enzymesactivating enzymeallosteric inhibitorcancerc-Myccovalent inhibitorE1KRasSUMOtherapeuticsubiquitin-like modification

Identifiers

PMID30581133
PMCPMC6524651
OpenAlexW2906239583

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.