Evidence map›Paper›PMID 29676157›Full record

ArticleBiochemistry2018

A High-Throughput Assay for Collagen Secretion Suggests an Unanticipated Role for Hsp90 in Collagen Production.

Madeline Y Wong, Ngoc Duc Doan, Andrew S DiChiara, Louis J Papa, Jaime H Cheah, Christian K Soule, Nicki Watson, John D Hulleman, Matthew D Shoulders

Abstract read
In one paragraph

Article in Biochemistry, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed
1.1field-weighted citation impact, top 23% 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

14 citing papers in PubMed, 19 citations in OpenAlex.

  1. The role of heat shock protein 90 in idiopathic pulmonary fibrosis: state of the art.European respiratory review : an official journal of the European Respiratory Society · 2025
    Review
  2. Article
  3. Review
  4. Article
  5. Article
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  7. Review
  8. Chemical Biology Framework to Illuminate Proteostasis.Annual review of biochemistry · 2020
    Review
  9. Article
  10. Review
  11. Genetic Engineering by DNA Recombineering.Current protocols in chemical biology · 2019
    Article
  12. Targeting defective proteostasis in the collagenopathies.Current opinion in chemical biology · 2019
    Review
  13. Article
  14. Collagen Prolyl 4-Hydroxylase as a Therapeutic Target.Journal of medicinal chemistry · 2018
    Review
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

9 authors at 4 institutions in 1 country.

Madeline Y WongDepartment of Chemistry , Massachusetts Institute of Technology , Cambridge , Massachusetts 02139 , United States.
Ngoc Duc DoanDepartment of Chemistry , Massachusetts Institute of Technology , Cambridge , Massachusetts 02139 , United States.
Andrew S DiChiaraDepartment of Chemistry , Massachusetts Institute of Technology , Cambridge , Massachusetts 02139 , United States.
Louis J PapaDepartment of Chemistry , Massachusetts Institute of Technology , Cambridge , Massachusetts 02139 , United States.
Jaime H CheahHigh-Throughput Sciences Facility, Koch Institute for Integrative Cancer Research , Massachusetts Institute of Technology , Cambridge , Massachusetts 02139 , United States.
Christian K SouleHigh-Throughput Sciences Facility, Koch Institute for Integrative Cancer Research , Massachusetts Institute of Technology , Cambridge , Massachusetts 02139 , United States.
Nicki WatsonW. M. Keck Microscopy Facility , The Whitehead Institute , Cambridge , Massachusetts 02142 , United States.
John D HullemanDepartments of Ophthalmology and Pharmacology , University of Texas Southwestern Medical Center , Dallas , Texas 75390 , United States.
Matthew D ShouldersDepartment of Chemistry , Massachusetts Institute of Technology , Cambridge , Massachusetts 02139 , United States.ORCID 0000-0002-6511-3431
Massachusetts Institute of Technology · USHigh Throughput Biology (United States) · USThe University of Texas Southwestern Medical Center · USWhitehead Institute for Biomedical Research · US

Funding

VIRUS PRODUCTION COREP30CA014051 · NCI · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI Angela Nicole Koehler · 1985 to 2026
$93.9M
Core Grant for Vision ResearchP30EY020799 · NEI · UT SOUTHWESTERN MEDICAL CENTER · PI NIEDERKORN, JERRY · 2010 to 2016
$4.1M
Defining and Modulating Mechanisms of Collagen ProteostasisR01AR071443 · NIAMS · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI SHOULDERS, MATTHEW DONALD · 2017 to 2021
$1.7M
Unveiling the Proteostasis Network of Normal and Disease_Causing Collagen_IR03AR067503 · NIAMS · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI SHOULDERS, MATTHEW DONALD · 2015 to 2017
$234k
A Novel Approach to Osteogenesis Imperfecta_ The Collagen Protein Folding ProblemF31AR067615 · NIAMS · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI DICHIARA, ANDREW STEPHEN · 2015 to 2017
$127k
NCI NIH HHS P30 CA014051NEI NIH HHS P30 EY020799NIAMS NIH HHS F31 AR067615NIAMS NIH HHS R01 AR071443NIAMS NIH HHS R03 AR067503
6 · The paper itself

Abstract

Collagen overproduction is a feature of fibrosis and cancer, while insufficient deposition of functional collagen molecules and/or the secretion of malformed collagen is common in genetic disorders like osteogenesis imperfecta. Collagen secretion is an appealing therapeutic target in these and other diseases, as secretion directly connects intracellular biosynthesis to collagen deposition and biological function in the extracellular matrix. However, small molecule and biological methods to tune collagen secretion are severely lacking. Their discovery could prove useful not only in the treatment of disease, but also in providing tools for better elucidating mechanisms of collagen biosynthesis. We developed a cell-based, high-throughput luminescent assay of collagen type I secretion and used it to screen for small molecules that selectively enhance or inhibit that process. Among several validated hits, the Hsp90 inhibitor 17-allylaminogeldanamycin (17-AAG) robustly decreases the secretion of collagen-I by our model cell line and by human primary cells. In these systems, 17-AAG and other pan-isoform Hsp90 inhibitors reduce collagen-I secretion post-translationally and are not global inhibitors of protein secretion. Surprisingly, the consequences of Hsp90 inhibitors cannot be attributed to inhibition of the endoplasmic reticulum's Hsp90 isoform, Grp94. Instead, collagen-I secretion likely depends on the activity of cytosolic Hsp90 chaperones, even though such chaperones cannot directly engage nascent collagen molecules. Our results highlight the value of a cell-based high-throughput screen for selective modulators of collagen secretion and suggest an unanticipated role for cytosolic Hsp90 in collagen secretion.

Indexed as

High-Throughput Screening AssaysBenzoquinonesCell LineCollagen Type IHSP90 Heat-Shock ProteinsHumansLactams, MacrocyclicMembrane GlycoproteinsProtein IsoformsBenzoquinonesCollagen Type IendoplasminHSP90 Heat-Shock ProteinsLactams, MacrocyclicMembrane GlycoproteinsProtein Isoformstanespimycin

Identifiers

PMID29676157
PMCPMC6231715
OpenAlexW2800069361

What OpenQuestion holds

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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.