Evidence map›Paper›PMID 30340023›Full record

ArticleMolecular cell2018

Cilia-Associated Oxysterols Activate Smoothened.

David R Raleigh, Navdar Sever, Pervinder K Choksi, Monika Abedin Sigg, Kelly M Hines, Bonne M Thompson, Daniel Elnatan, Priyadarshini Jaishankar, Paola Bisignano, Francesc R Garcia-Gonzalo and 11 more

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

Article in Molecular cell, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 76 papers.

0numbers the graph read from it
0cells of the map it votes in
76citing papers in PubMed
6.9field-weighted citation impact, top 2% 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

76 citing papers in PubMed, 130 citations in OpenAlex.

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16 more citing papers are in PubMed but not listed here.

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

21 authors at 8 institutions in 2 countries.

David R RaleighDepartment of Radiation Oncology, University of California, San Francisco, San Francisco, CA, USA; Department of Neurological Surgery, University of California, San Francisco, San Francisco, CA, USA; Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA, USA.
Navdar SeverDepartment of Biochemistry, Stanford University School of Medicine, Stanford, CA, USA; Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA, USA.
Pervinder K ChoksiDepartment of Radiation Oncology, University of California, San Francisco, San Francisco, CA, USA; Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA, USA.
Monika Abedin SiggDepartment of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA, USA.
Kelly M HinesDepartment of Medicinal Chemistry, University of Washington, Seattle, WA, USA.
Bonne M ThompsonCenter for Human Nutrition, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Daniel ElnatanDepartment of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA, USA.
Priyadarshini JaishankarDepartment of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, CA, USA; Small Molecule Discovery Center, University of California, San Francisco, San Francisco, CA, USA.
Paola BisignanoDepartment of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, CA, USA; Cardiovascular Research Institute, University of California, San Francisco, San Francisco, CA, USA.
Francesc R Garcia-GonzaloDepartment of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA, USA.
Alexis Leigh KrupDepartment of Radiation Oncology, University of California, San Francisco, San Francisco, CA, USA; Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA, USA.
Markus EberlDepartment of Dermatology, University of Michigan, Ann Arbor, MI, USA.
Eamon F X ByrneDivision of Structural Biology, Wellcome Centre for Human Genetics, University of Oxford, Oxford, UK.
Christian SieboldDivision of Structural Biology, Wellcome Centre for Human Genetics, University of Oxford, Oxford, UK.
Sunny Y WongDepartment of Dermatology, University of Michigan, Ann Arbor, MI, USA.
Adam R RensloDepartment of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, CA, USA; Small Molecule Discovery Center, University of California, San Francisco, San Francisco, CA, USA.
Michael GrabeDepartment of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, CA, USA; Cardiovascular Research Institute, University of California, San Francisco, San Francisco, CA, USA.
Jeffrey G McDonaldCenter for Human Nutrition, University of Texas Southwestern Medical Center, Dallas, TX, USA; Department of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Libin XuDepartment of Medicinal Chemistry, University of Washington, Seattle, WA, USA.
Philip A BeachyDepartment of Biochemistry, Stanford University School of Medicine, Stanford, CA, USA; Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA, USA; Department of Urology and Department of Developmental Biology, Stanford University School of Medicine, Stanford, CA, USA.
Jeremy F ReiterDepartment of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA, USA; Cardiovascular Research Institute, University of California, San Francisco, San Francisco, CA, USA. Electronic address: jeremy.reiter@ucsf.edu.
University of California, San Francisco · USStanford University · USThe University of Texas Southwestern Medical Center · USUniversity of Michigan–Ann Arbor · USUniversity of Washington · USCentre for Human Genetics · GBNeurological Surgery · USUniversity of Oxford · GB

Funding

TRANSCRIPTIONAL REGULATION OF LDL RECEPTOR PROMOTERP01HL020948 · NHLBI · UT SOUTHWESTERN MEDICAL CENTER · PI HORTON, JAY D. · 1985 to 2021
$103.1M
UCSF Nutrition Obesity Research CenterP30DK098722 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI CHRISTIAN VAISSE · 2015 to 2026
$14.6M
MOLECULAR AND CELLULAR BASIS OF CARDIOVASCULAR DISEASET32HL007731 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Brian L Black · 1992 to 2026
$12.4M
Hedgehog signaling at the cell's antenna: Smoothened and the primary ciliumR01AR054396 · NIAMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Jeremy F Reiter · 2007 to 2026
$9.0M
Obesity in Ciliopathies: How Neuronal Primary Cilia Control AppetiteR01DK106404 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI REITER, JEREMY F, VAISSE, CHRISTIAN · 2016 to 2025
$6.6M
Molecular mechanisms of Hedgehog receptor functionR01GM102498 · NIGMS · STANFORD UNIVERSITY · PI PHILIP A BEACHY · 2012 to 2026
$4.5M
The Hair Follicle Infundibulum: A Potential Mediator of Skin Barrier FunctionR01AR065409 · NIAMS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Sunny Y Wong · 2014 to 2026
$3.8M
Transition zone control of ciliary signalingR01GM095941 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI REITER, JEREMY F · 2011 to 2018
$3.4M
Computational Studies of Sodium SymportersR01GM089740 · NIGMS · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI GRABE, MICHAEL · 2011 to 2020
$2.8M
Oxysterols in SLOS Neurodevelopment: Pathological Role and TherapyR01HD092659 · NICHD · UNIVERSITY OF WASHINGTON · PI XU, LIBIN · 2017 to 2021
$1.9M
Understanding How Ciliary Hedgehog Signaling Causes MedulloblastomaK08CA212279 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI RALEIGH, DAVID R · 2017 to 2021
$886k
Cancer Research UK 14414Cancer Research UK 26752Cancer Research UK A14414Cancer Research UK C20724European Research Council 647278Howard Hughes Medical InstituteNCI NIH HHS K08 CA212279NHLBI NIH HHS P01 HL020948NHLBI NIH HHS T32 HL007731NIAMS NIH HHS R01 AR054396NIAMS NIH HHS R01 AR065409NICHD NIH HHS R01 HD092659NIDDK NIH HHS P30 DK098722NIDDK NIH HHS R01 DK106404NIGMS NIH HHS R01 GM089740NIGMS NIH HHS R01 GM095941NIGMS NIH HHS R01 GM102498
6 · The paper itself

Abstract

Primary cilia are required for Smoothened to transduce vertebrate Hedgehog signals, but how Smoothened accumulates in cilia and is activated is incompletely understood. Here, we identify cilia-associated oxysterols that promote Smoothened accumulation in cilia and activate the Hedgehog pathway. Our data reveal that cilia-associated oxysterols bind to two distinct Smoothened domains to modulate Smoothened accumulation in cilia and tune the intensity of Hedgehog pathway activation. We find that the oxysterol synthase HSD11β2 participates in the production of Smoothened-activating oxysterols and promotes Hedgehog pathway activity. Inhibiting oxysterol biosynthesis impedes oncogenic Hedgehog pathway activation and attenuates the growth of Hedgehog pathway-associated medulloblastoma, suggesting that targeted inhibition of Smoothened-activating oxysterol production may be therapeutically useful for patients with Hedgehog-associated cancers.

Indexed as

AnimalsCell LineCiliaHedgehog ProteinsHEK293 CellsHumansMiceNIH 3T3 CellsOxysterolsSignal TransductionHedgehog ProteinsOxysterolsCBPciliaHedgehogHSD11β2lipidmedulloblastomaoxysterolprimary ciliumSmoothenedsterol

Identifiers

PMID30340023
PMCPMC6503851
OpenAlexW2896277604

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Registered trials

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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.