Suppressor of fused impedes Ci/Gli nuclear import by opposing trn/kapβ2 in hedgehog signaling

Qing Shi, Yuhong Han, Jin Jiang

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

The Hedgehog (Hh) family of secreted proteins governs many key developmental processes by regulating Ci/Gli transcription factors at multiple levels including nuclear-cytoplasmic shuttling. Here, we investigate the mechanism underlying the regulation of Ci/Gli subcellular localization by identifying and characterizing a novel nuclear localization sequence (NLS) in the N-terminal conserved domain of Ci/Gli that matches the PY-NLS consensus. We demonstrate that the PY-NLS functions in parallel with a previously identified bipartite NLS to promote nuclear localization and activity of full-length Ci. We find that Transportin (Trn), the Drosophila homolog of Kapβ2, is responsible for PY-NLS-mediated nuclear localization of Ci. Furthermore, we show that the tumor suppressor and conserved Hh pathway component Suppressor of fused (Sufu) opposes Trn-mediated Ci nuclear import by masking its PY-NLS. Finally, we provide evidence that Gli proteins also contain a functional PY-NLS and that mammal Sufu uses a similar mechanism to regulate nuclear translocation of Gli. Our study not only provides a mechanistic insight into how Sufu regulates Hh signaling and the subcellular localization of Ci/Gli, but also reveals a role for Trn/Kapb2 in developmental regulation

Original languageEnglish (US)
Pages (from-to)1092-1103
Number of pages12
JournalJournal of Cell Science
Volume127
Issue number5
DOIs
StatePublished - Mar 2014

Fingerprint

Karyopherins
Cell Nucleus Active Transport
Hedgehogs
Consensus Sequence
Drosophila
Mammals
Transcription Factors
Neoplasms
Proteins

Keywords

  • Ci
  • Gli
  • Hedgehog
  • Py-nls
  • Sufu
  • Transportin

ASJC Scopus subject areas

  • Cell Biology

Cite this

Suppressor of fused impedes Ci/Gli nuclear import by opposing trn/kapβ2 in hedgehog signaling. / Shi, Qing; Han, Yuhong; Jiang, Jin.

In: Journal of Cell Science, Vol. 127, No. 5, 03.2014, p. 1092-1103.

Research output: Contribution to journalArticle

@article{96f64c843aa84ed18fcb31542c1794ac,
title = "Suppressor of fused impedes Ci/Gli nuclear import by opposing trn/kapβ2 in hedgehog signaling",
abstract = "The Hedgehog (Hh) family of secreted proteins governs many key developmental processes by regulating Ci/Gli transcription factors at multiple levels including nuclear-cytoplasmic shuttling. Here, we investigate the mechanism underlying the regulation of Ci/Gli subcellular localization by identifying and characterizing a novel nuclear localization sequence (NLS) in the N-terminal conserved domain of Ci/Gli that matches the PY-NLS consensus. We demonstrate that the PY-NLS functions in parallel with a previously identified bipartite NLS to promote nuclear localization and activity of full-length Ci. We find that Transportin (Trn), the Drosophila homolog of Kapβ2, is responsible for PY-NLS-mediated nuclear localization of Ci. Furthermore, we show that the tumor suppressor and conserved Hh pathway component Suppressor of fused (Sufu) opposes Trn-mediated Ci nuclear import by masking its PY-NLS. Finally, we provide evidence that Gli proteins also contain a functional PY-NLS and that mammal Sufu uses a similar mechanism to regulate nuclear translocation of Gli. Our study not only provides a mechanistic insight into how Sufu regulates Hh signaling and the subcellular localization of Ci/Gli, but also reveals a role for Trn/Kapb2 in developmental regulation",
keywords = "Ci, Gli, Hedgehog, Py-nls, Sufu, Transportin",
author = "Qing Shi and Yuhong Han and Jin Jiang",
year = "2014",
month = "3",
doi = "10.1242/jcs.142828",
language = "English (US)",
volume = "127",
pages = "1092--1103",
journal = "Journal of Cell Science",
issn = "0021-9533",
publisher = "Company of Biologists Ltd",
number = "5",

}

TY - JOUR

T1 - Suppressor of fused impedes Ci/Gli nuclear import by opposing trn/kapβ2 in hedgehog signaling

AU - Shi, Qing

AU - Han, Yuhong

AU - Jiang, Jin

PY - 2014/3

Y1 - 2014/3

N2 - The Hedgehog (Hh) family of secreted proteins governs many key developmental processes by regulating Ci/Gli transcription factors at multiple levels including nuclear-cytoplasmic shuttling. Here, we investigate the mechanism underlying the regulation of Ci/Gli subcellular localization by identifying and characterizing a novel nuclear localization sequence (NLS) in the N-terminal conserved domain of Ci/Gli that matches the PY-NLS consensus. We demonstrate that the PY-NLS functions in parallel with a previously identified bipartite NLS to promote nuclear localization and activity of full-length Ci. We find that Transportin (Trn), the Drosophila homolog of Kapβ2, is responsible for PY-NLS-mediated nuclear localization of Ci. Furthermore, we show that the tumor suppressor and conserved Hh pathway component Suppressor of fused (Sufu) opposes Trn-mediated Ci nuclear import by masking its PY-NLS. Finally, we provide evidence that Gli proteins also contain a functional PY-NLS and that mammal Sufu uses a similar mechanism to regulate nuclear translocation of Gli. Our study not only provides a mechanistic insight into how Sufu regulates Hh signaling and the subcellular localization of Ci/Gli, but also reveals a role for Trn/Kapb2 in developmental regulation

AB - The Hedgehog (Hh) family of secreted proteins governs many key developmental processes by regulating Ci/Gli transcription factors at multiple levels including nuclear-cytoplasmic shuttling. Here, we investigate the mechanism underlying the regulation of Ci/Gli subcellular localization by identifying and characterizing a novel nuclear localization sequence (NLS) in the N-terminal conserved domain of Ci/Gli that matches the PY-NLS consensus. We demonstrate that the PY-NLS functions in parallel with a previously identified bipartite NLS to promote nuclear localization and activity of full-length Ci. We find that Transportin (Trn), the Drosophila homolog of Kapβ2, is responsible for PY-NLS-mediated nuclear localization of Ci. Furthermore, we show that the tumor suppressor and conserved Hh pathway component Suppressor of fused (Sufu) opposes Trn-mediated Ci nuclear import by masking its PY-NLS. Finally, we provide evidence that Gli proteins also contain a functional PY-NLS and that mammal Sufu uses a similar mechanism to regulate nuclear translocation of Gli. Our study not only provides a mechanistic insight into how Sufu regulates Hh signaling and the subcellular localization of Ci/Gli, but also reveals a role for Trn/Kapb2 in developmental regulation

KW - Ci

KW - Gli

KW - Hedgehog

KW - Py-nls

KW - Sufu

KW - Transportin

UR - http://www.scopus.com/inward/record.url?scp=84896861295&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84896861295&partnerID=8YFLogxK

U2 - 10.1242/jcs.142828

DO - 10.1242/jcs.142828

M3 - Article

VL - 127

SP - 1092

EP - 1103

JO - Journal of Cell Science

JF - Journal of Cell Science

SN - 0021-9533

IS - 5

ER -