Evidence map›Paper›PMID 28777795›Full record

ArticlePLoS biology2017

Regulation of Gli ciliary localization and Hedgehog signaling by the PY-NLS/karyopherin-β2 nuclear import system.

Yuhong Han, Yue Xiong, Xuanming Shi, Jiang Wu, Yun Zhao, Jin Jiang

Open access · goldAbstract read
In one paragraph

Article in PLoS biology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.

0numbers the graph read from it
0cells of the map it votes in
37citing papers in PubMed
2.0field-weighted citation impact, top 13% 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

37 citing papers in PubMed, 53 citations in OpenAlex.

  1. Review
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  12. Hedgehog signaling mechanism and role in cancer.Seminars in cancer biology · 2022
    Review
  13. Article
  14. Review
  15. Review
  16. Ci/Gli Phosphorylation by the Fused/Ulk Family Kinases.Methods in molecular biology (Clifton, N.J.) · 2022
    Article
  17. Gli Phosphorylation Code in Hedgehog Signal Transduction.Frontiers in cell and developmental biology · 2022
    Review
  18. Review
  19. Review
  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

6 authors at 2 institutions in 2 countries.

Yuhong HanDepartment of Molecular Biology, University of Texas Southwestern Medical Center at Dallas, Dallas, Texas, United States of America.ORCID http://orcid.org/0000-0001-8933-4637
Yue XiongState Key Laboratory of Cell Biology, CAS Center for Excellence in Molecular Cell Science, Innovation Center for Cell Signaling Network, Institute of Biochemistry and Cell Biology, Shanghai Institute of Life Sciences, CAS, School of Life Science and Technology, ShanghaiTech University, Shanghai, China.
Xuanming ShiDepartment of Physiology, University of Texas Southwestern Medical Center at Dallas, Dallas, Texas, United States of America.
Jiang WuDepartment of Physiology, University of Texas Southwestern Medical Center at Dallas, Dallas, Texas, United States of America.
Yun ZhaoState Key Laboratory of Cell Biology, CAS Center for Excellence in Molecular Cell Science, Innovation Center for Cell Signaling Network, Institute of Biochemistry and Cell Biology, Shanghai Institute of Life Sciences, CAS, School of Life Science and Technology, ShanghaiTech University, Shanghai, China.
Jin JiangDepartment of Molecular Biology, University of Texas Southwestern Medical Center at Dallas, Dallas, Texas, United States of America.
The University of Texas Southwestern Medical Center · USShanghaiTech University · CN

Funding

Cell signaling in development and regenerationR35GM118063 · NIGMS · UT SOUTHWESTERN MEDICAL CENTER · PI Jin Jiang · 2016 to 2026
$9.4M
REGULATION OF HEDGEHOG SIGNALING IN DROSOPHILAR01GM061269 · NIGMS · UT SOUTHWESTERN MEDICAL CENTER · PI JIANG, JIN · 2000 to 2016
$4.2M
Regulation of Hh/Ci signaling by Cos2 and its partnersR01GM067045 · NIGMS · UT SOUTHWESTERN MEDICAL CENTER · PI JIANG, JIN · 2003 to 2015
$4.0M
Role of Brg1 in Activity-Induced Neuronal Gene Expression and Synaptic PlasticityR01NS096068 · NINDS · UT SOUTHWESTERN MEDICAL CENTER · PI WU, JIANG · 2016 to 2020
$1.8M
A Novel Non-Cell Autonomous Tumor Suppressor Function of H3K27me3 Demethylase UTX/Kdm6a in MedulloblastomaR21NS104596 · NINDS · UT SOUTHWESTERN MEDICAL CENTER · PI WU, JIANG · 2017 to 2018
$446k
NIGMS NIH HHS R01 GM061269NIGMS NIH HHS R01 GM067045NIGMS NIH HHS R35 GM118063NINDS NIH HHS R01 NS096068NINDS NIH HHS R21 NS104596
6 · The paper itself

Abstract

Hedgehog (Hh) signaling in vertebrates depends on primary cilia. Upon stimulation, Hh pathway components, including Gli transcription factors, accumulate at primary cilia to transduce the Hh signal, but the mechanisms underlying their ciliary targeting remains largely unknown. Here, we show that the PY-type nuclear localization signal (PY-NLS)/karyopherinβ2 (Kapβ2) nuclear import system regulates Gli ciliary localization and Hh pathway activation. Mutating the PY-NLS in Gli or knockdown of Kapβ2 diminished Gli ciliary localization. Kapβ2 is required for the formation of Gli activator (GliA) in wild-type but not in Sufu mutant cells. Knockdown of Kapβ2 affected Hh signaling in zebrafish embryos, as well as in vitro cultured cerebellum granule neuron progenitors (CGNPs) and SmoM2-driven medulloblastoma cells. Furthermore, Kapβ2 depletion impaired the growth of cultured medulloblastoma cells, which was rescued by Gli overexpression. Interestingly, Kapβ2 is a transcriptional target of the Hh pathway, thus forming a positive feedback loop for Gli activation. Our study unravels the molecular mechanism and cellular machinery regulating Gli ciliary localization and identifies Kapβ2 as a critical regulator of the Hh pathway and a potential drug target for Hh-driven cancers.

Indexed as

Nuclear Localization SignalsAnimalsAnimals, Genetically Modifiedbeta KaryopherinsCerebellar NeoplasmsCiliaEmbryo, NonmammalianFeedback, PhysiologicalHedgehog ProteinsMedulloblastomaMiceNIH 3T3 CellsZebrafishZinc Finger Protein GLI1beta KaryopherinsHedgehog ProteinsNuclear Localization SignalsZinc Finger Protein GLI1

Identifiers

PMID28777795
PMCPMC5544186
OpenAlexW2743472536

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.