Evidence map›Paper›PMID 25403183›Full record

ArticleGenes & development2014

Regulation of Sufu activity by p66β and Mycbp provides new insight into vertebrate Hedgehog signaling.

Chuwen Lin, Erica Yao, Kevin Wang, Yoko Nozawa, Hirohito Shimizu, Jeffrey R Johnson, Jau-Nian Chen, Nevan J Krogan, Pao-Tien Chuang

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

Article in Genes & development, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.

0numbers the graph read from it
0cells of the map it votes in
35citing papers in PubMed
–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

35 citing papers in PubMed, 45 citations in OpenAlex.

  1. Review
  2. Review
  3. Review
  4. Article
  5. Hedgehog signaling mechanism and role in cancer.Seminars in cancer biology · 2022
    Review
  6. Article
  7. Review
  8. Review
  9. Proteostasis in the Hedgehog signaling pathway.Seminars in cell & developmental biology · 2019
    Review
  10. Article
  11. Review
  12. Article
  13. Review
  14. Article
  15. Review
  16. Review
  17. Article
  18. Article
  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

9 authors at 2 institutions in 1 country.

Chuwen LinCardiovascular Research Institute, University of California at San Francisco, San Francisco, California 94158, USA;
Erica YaoCardiovascular Research Institute, University of California at San Francisco, San Francisco, California 94158, USA;
Kevin WangDepartment of Molecular, Cell, and Developmental Biology, University of California at Los Angeles, Los Angeles, California 90095, USA;
Yoko NozawaCardiovascular Research Institute, University of California at San Francisco, San Francisco, California 94158, USA;
Hirohito ShimizuDepartment of Molecular, Cell, and Developmental Biology, University of California at Los Angeles, Los Angeles, California 90095, USA;
Jeffrey R JohnsonDepartment of Cellular and Molecular Pharmacology, University of California at San Francisco, San Francisco, California 94158.
Jau-Nian ChenDepartment of Molecular, Cell, and Developmental Biology, University of California at Los Angeles, Los Angeles, California 90095, USA;
Nevan J KroganDepartment of Cellular and Molecular Pharmacology, University of California at San Francisco, San Francisco, California 94158.
Pao-Tien ChuangCardiovascular Research Institute, University of California at San Francisco, San Francisco, California 94158, USA; pao-tien.chuang@ucsf.edu.
University of California, San Francisco · USUniversity of California, Los Angeles · US

Funding

Rewiring Therapeutic Cells: User-Controlled T Cells and Stem CellsP50GM081879 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI LIM, WENDELL A · 2010 to 2017
$19.0M
Comparative Analysis of Genetic Interaction NetworksR01GM084279 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI IDEKER, TREY, KROGAN, NEVAN J · 2008 to 2017
$3.9M
Patterning of the Primitive Heart Tube in ZebrafishR01HL081700 · NHLBI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI CHEN, JAU-NIAN · 2007 to 2010
$1.5M
Elucidating the molecular mechanisms regulating embryonic cardiac rhythmicityR01HL096980 · NHLBI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI CHEN, JAU-NIAN · 2010 to 2013
$1.5M
Molecular Mechanisms of Mammalian Hedgehog Signal TransductionR01GM085097 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI CHUANG, PAO-TIEN · 2008 to 2011
$1.2M
NHLBI NIH HHS R01 HL081700NHLBI NIH HHS R01 HL096980NIGMS NIH HHS P50 GM081879NIGMS NIH HHS R01 GM084279NIGMS NIH HHS R01 GM085097
6 · The paper itself

Abstract

Control of Gli function by Suppressor of Fused (Sufu), a major negative regulator, is a key step in mammalian Hedgehog (Hh) signaling, but how this is achieved in the nucleus is unknown. We found that Hh signaling results in reduced Sufu protein levels and Sufu dissociation from Gli proteins in the nucleus, highlighting critical functions of Sufu in the nucleus. Through a proteomic approach, we identified several Sufu-interacting proteins, including p66β (a member of the NuRD [nucleosome remodeling and histone deacetylase] repressor complex) and Mycbp (a Myc-binding protein). p66β negatively and Mycbp positively regulate Hh signaling in cell-based assays and zebrafish. They function downstream from the membrane receptors, Patched and Smoothened, and the primary cilium. Sufu, p66β, Mycbp, and Gli are also detected on the promoters of Hh targets in a dynamic manner. Our results support a new model of Hh signaling in the nucleus. Sufu recruits p66β to block Gli-mediated Hh target gene expression. Meanwhile, Mycbp forms a complex with Gli and Sufu without Hh stimulation but remains inactive. Hh pathway activation leads to dissociation of Sufu/p66β from Gli, enabling Mycbp to promote Gli protein activity and Hh target gene expression. These studies provide novel insight into how Sufu controls Hh signaling in the nucleus.

Indexed as

Gene Expression RegulationSignal TransductionAnimalsCell NucleusCytoplasmGene Knockdown TechniquesHedgehog ProteinsHEK293 CellsHumansKruppel-Like Transcription FactorsMiceMutationNIH 3T3 CellsProtein BindingProteomicsRepressor ProteinsAmy1 protein, mouseGli1 protein, mouseHedgehog ProteinsKruppel-Like Transcription FactorsRepressor ProteinsSalivary alpha-AmylasesSufu protein, mouseZinc Finger Protein GLI1GliHh signalingMycbpp66βSufu

Identifiers

PMID25403183
PMCPMC4233246
OpenAlexW2019161243

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.