Evidence map›Paper›PMID 25644602›Full record

ArticleGenes & development2015

Bifurcating action of Smoothened in Hedgehog signaling is mediated by Dlg5.

Yong Chun Chong, Randall K Mann, Chen Zhao, Masaki Kato, Philip A Beachy

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

Article in Genes & development, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
22citing papers in PubMed, 1 pooled it
–field-weighted citation impact
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

22 citing papers in PubMed, 1 synthesis or guideline pooled it, 34 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Article
  4. Article
  5. Article
  6. Article
  7. Hedgehog signaling mechanism and role in cancer.Seminars in cancer biology · 2022
    Review
  8. Article
  9. Article
  10. Journal of medical genetics · 2021
    Article
  11. Article
  12. Article
  13. Review
  14. Review
  15. Article
  16. Review
  17. Article
  18. Article
  19. Article
  20. Smoothened Regulation: A Tale of Two Signals.Trends in pharmacological sciences · 2016
    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

5 authors at 2 institutions in 1 country.

Yong Chun ChongInstitute for Stem Cell Biology and Regenerative Medicine, Stanford University, Stanford, California 94305, USA; Department of Developmental Biology, Stanford University, Stanford, California 94305, USA; Department of Biochemistry, Stanford University, Stanford, California 94305, USA;
Randall K MannInstitute for Stem Cell Biology and Regenerative Medicine, Stanford University, Stanford, California 94305, USA; Department of Developmental Biology, Stanford University, Stanford, California 94305, USA; Department of Biochemistry, Stanford University, Stanford, California 94305, USA;
Chen ZhaoInstitute for Stem Cell Biology and Regenerative Medicine, Stanford University, Stanford, California 94305, USA; Department of Developmental Biology, Stanford University, Stanford, California 94305, USA; Department of Biochemistry, Stanford University, Stanford, California 94305, USA;
Masaki KatoInstitute for Stem Cell Biology and Regenerative Medicine, Stanford University, Stanford, California 94305, USA; Department of Developmental Biology, Stanford University, Stanford, California 94305, USA;
Philip A BeachyInstitute for Stem Cell Biology and Regenerative Medicine, Stanford University, Stanford, California 94305, USA; Department of Developmental Biology, Stanford University, Stanford, California 94305, USA; Department of Biochemistry, Stanford University, Stanford, California 94305, USA; Howard Hughes Medical Institute, Stanford University, Stanford, California 94305, USA pbeachy@stanford.edu.
Stanford University · USCalifornia Institute for Regenerative Medicine · US

Funding

Molecular mechanisms of Hedgehog receptor functionR01GM102498 · NIGMS · STANFORD UNIVERSITY · PI PHILIP A BEACHY · 2012 to 2026
$4.5M
Howard Hughes Medical InstituteNIGMS NIH HHS R01 GM102498NIGMS NIH HHS R01GM102498
6 · The paper itself

Abstract

Binding of the Hedgehog (Hh) protein signal to its receptor, Patched, induces accumulation of the seven-pass transmembrane protein Smoothened (Smo) within the primary cilium and of the zinc finger transcription factor Gli2 at the ciliary tip, resulting ultimately in Gli-mediated changes in nuclear gene expression. However, the mechanism by which pathway activation is communicated from Smo to Gli2 is not known. In an effort to elucidate this mechanism, we identified Dlg5 (Discs large, homolog 5) in a biochemical screen for proteins that preferentially interact with activated Smo. We found that disruption of Smo-Dlg5 interactions or depletion of endogenous Dlg5 leads to diminished Hh pathway response without a significant impact on Smo ciliary accumulation. We also found that Dlg5 is localized at the basal body, where it associates with another pathway component, Kif7. We show that Dlg5 is required for Hh-induced enrichment of Kif7 and Gli2 at the tip of the cilium but is dispensable for Gpr161 exit from the cilium and the consequent suppression of Gli3 processing into its repressor form. Our findings suggest a bifurcation of Smo activity in Hh response, with a Dlg5-independent arm for suppression of Gli repressor formation and a second arm involving Smo interaction with Dlg5 for Gli activation.

Indexed as

Signal TransductionAmino Acid MotifsAnimalsBasal BodiesCell LineCiliaGuanylate KinasesHedgehog ProteinsHEK293 CellsHumansKinesinsKruppel-Like Transcription FactorsMembrane ProteinsMiceNerve Tissue ProteinsNIH 3T3 CellsDlg5 protein, mouseGli2 protein, mouseGli3 protein, mouseGuanylate KinasesHedgehog ProteinsKif7 protein, mouseKinesinsKruppel-Like Transcription FactorsMembrane ProteinsNerve Tissue ProteinsReceptors, G-Protein-CoupledSmoothened ReceptorSmo protein, mouseZinc Finger Protein Gli2Zinc Finger Protein Gli3basal bodyDlg5GliHedgehogKif7Smoothened

Identifiers

PMID25644602
PMCPMC4318143
OpenAlexW2130857754

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
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.