Evidence map›Paper›PMID 26320861›Full record

ArticleChemistry & biology2015

Small-Molecule Reactivation of Mutant p53 to Wild-Type-like p53 through the p53-Hsp40 Regulatory Axis.

Masatsugu Hiraki, So-Young Hwang, Shugeng Cao, Timothy R Ramadhar, Sanguine Byun, Kyoung Wan Yoon, Jung Hyun Lee, Kiki Chu, Aditi U Gurkar, Vihren Kolev and 7 more

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

Article in Chemistry & biology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers.

0numbers the graph read from it
0cells of the map it votes in
53citing papers in PubMed
3.4field-weighted citation impact, top 6% 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

53 citing papers in PubMed, 79 citations in OpenAlex.

  1. Article
  2. Article
  3. Review
  4. Natural products that target p53 for cancer therapy.Journal of natural medicines · 2025
    Review
  5. Article
  6. Review
  7. Review
  8. Review
  9. Article
  10. Review
  11. Review
  12. Review
  13. Article
  14. Review
  15. Small-molecule correctors and stabilizers to target p53.Trends in pharmacological sciences · 2023
    Review
  16. Review
  17. Review
  18. Review
  19. Article
  20. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

17 authors at 4 institutions in 1 country.

Masatsugu HirakiCutaneous Biology Research Center, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129, USA.
So-Young HwangCutaneous Biology Research Center, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129, USA.
Shugeng CaoDepartment of Pharmaceutical Sciences, Daniel K. Inouye College of Pharmacy, University of Hawaii at Hilo, 34 Rainbow Drive, Hilo, HI 96720, USA; Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA.
Timothy R RamadharDepartment of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA.
Sanguine ByunCutaneous Biology Research Center, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129, USA.
Kyoung Wan YoonCutaneous Biology Research Center, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129, USA.
Jung Hyun LeeCutaneous Biology Research Center, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129, USA.
Kiki ChuCutaneous Biology Research Center, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129, USA.
Aditi U GurkarCutaneous Biology Research Center, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129, USA.
Vihren KolevCutaneous Biology Research Center, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129, USA.
Jianming ZhangCutaneous Biology Research Center, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129, USA.
Takushi NambaCutaneous Biology Research Center, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129, USA.
Maureen E MurphyProgram in Molecular and Cellular Oncogenesis, The Wistar Institute, Philadelphia, PA 19104, USA.
David J NewmanNatural Products Branch, Developmental Therapeutics Program, Division of Cancer Treatment and Diagnosis, Frederick National Laboratory for Cancer Research, Frederick, MD 21702, USA.
Anna MandinovaCutaneous Biology Research Center, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129, USA; Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA.
Jon ClardyDepartment of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA. Electronic address: jon_clardy@hms.harvard.edu.
Sam W LeeCutaneous Biology Research Center, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129, USA; Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA. Electronic address: swlee@mgh.harvard.edu.
Harvard University · USBroad Institute · USFrederick National Laboratory for Cancer Research · USThe Wistar Institute · US

Funding

Tumor Microenvironment and MetastasisP30CA010815 · NCI · WISTAR INSTITUTE · PI Luis J Montaner · 1985 to 2026
$75.9M
Targeting the MAP and PI3 Kinase Pathways in MelanomaP01CA114046 · NCI · WISTAR INSTITUTE · PI MURPHY, MAUREEN E. · 2008 to 2023
$37.1M
PW1--A mediator of cell survival by NFKB and cell death by p53P01CA080058 · NCI · MOUNT SINAI SCHOOL OF MEDICINE OF NYU · PI AARONSON, STUART A · 2000 to 2016
$20.2M
The ARF Tumor SuppressorR01CA139319 · NCI · WISTAR INSTITUTE · PI MURPHY, MAUREEN E. · 2010 to 2019
$3.9M
Molecule-to-gene approaches to new natural productsR01GM086258 · NIGMS · HARVARD MEDICAL SCHOOL · PI CLARDY, JON · 2008 to 2016
$3.6M
Targeting ROS by a p53-activating agent for selective killing of cancer cellsR01CA142805 · NCI · MASSACHUSETTS GENERAL HOSPITAL · PI LEE, SAM W · 2010 to 2014
$1.7M
p53-GAMT pathway in cancer cell metabolism and DNA damage-induced carcinogenesisR01CA149477 · NCI · MASSACHUSETTS GENERAL HOSPITAL · PI LEE, SAM W · 2010 to 2014
$1.7M
Discovery of Potential Therapeutic Agents from Insect-Associated Symbiotic BacterF32GM108415 · NIGMS · HARVARD MEDICAL SCHOOL · PI RAMADHAR, TIMOTHY RAMESAR · 2014 to 2015
$106k
NCI NIH HHS CA142805NCI NIH HHS CA80058NCI NIH HHS P01 CA080058NCI NIH HHS P01 CA114046NCI NIH HHS P30 CA010815NCI NIH HHS R01 CA139319NCI NIH HHS R01 CA142805NCI NIH HHS R01 CA149477NIGMS NIH HHS F32 GM108415NIGMS NIH HHS GM086258NIGMS NIH HHS GM108415NIGMS NIH HHS R01 GM086258
6 · The paper itself

Abstract

TP53 is the most frequently mutated gene in human cancer, and small-molecule reactivation of mutant p53 function represents an important anticancer strategy. A cell-based, high-throughput small-molecule screen identified chetomin (CTM) as a mutant p53 R175H reactivator. CTM enabled p53 to transactivate target genes, restored MDM2 negative regulation, and selectively inhibited the growth of cancer cells harboring mutant p53 R175H in vitro and in vivo. We found that CTM binds to Hsp40 and increases the binding capacity of Hsp40 to the p53 R175H mutant protein, causing a potential conformational change to a wild-type-like p53. Thus, CTM acts as a specific reactivator of the p53 R175H mutant form through Hsp40. These results provide new insights into the mechanism of reactivation of this specific p53 mutant.

Indexed as

AnimalsAntineoplastic AgentsCell Line, TumorDisulfidesDrug Screening Assays, AntitumorHCT116 CellsHigh-Throughput Screening AssaysHSP40 Heat-Shock ProteinsHumansIndole AlkaloidsMiceMice, NudeMutationSmall Molecule LibrariesTumor Suppressor Protein p53Xenograft Model Antitumor AssaysAntineoplastic AgentschetominDisulfidesDNAJB1 protein, humanHSP40 Heat-Shock ProteinsIndole AlkaloidsSmall Molecule LibrariesTP53 protein, humanTumor Suppressor Protein p53

Identifiers

PMID26320861
PMCPMC4670040
OpenAlexW1763368382

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.