Suppressor of Fused inhibits mammalian Hedgehog signaling in the absence of cilia

Jinping Jia, Åsa Kolterud, Huiqing Zeng, Amber Hoover, Stephan Teglund, Rune Toftgård, Aimin Liu

Research output: Contribution to journalArticle

99 Citations (Scopus)

Abstract

The Hedgehog (Hh) family of secreted proteins regulates mammalian development and cancer formation through Gli transcription factors, which exist in both activator and repressor forms. In vertebrates, the primary cilia play an essential role in Hh signal transduction and are required for both the activator and repressor activities of Gli proteins. In the current study, we demonstrate that mouse Suppressor of Fused (Sufu) interacts with Gli proteins and inhibits Gli activator activity in the absence of cilia. Removal of Sufu in both Smoothened (Smo) and Ift88 mutants, respectively, leads to full activation of Hh signaling, suggesting that Smo-mediated repression of Sufu, but not the inhibitory function of Sufu, requires cilia. Finally, we show that Sufu is important for proper activator/repressor ratio of Gli3 protein in mice, both in the presence and absence of cilia.

Original languageEnglish (US)
Pages (from-to)452-460
Number of pages9
JournalDevelopmental biology
Volume330
Issue number2
DOIs
StatePublished - Jun 15 2009

Fingerprint

Hedgehogs
Cilia
Vertebrates
Signal Transduction
Transcription Factors
Neoplasms
Proteins
Zinc Finger Protein GLI1

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Developmental Biology
  • Cell Biology

Cite this

Jia, Jinping ; Kolterud, Åsa ; Zeng, Huiqing ; Hoover, Amber ; Teglund, Stephan ; Toftgård, Rune ; Liu, Aimin. / Suppressor of Fused inhibits mammalian Hedgehog signaling in the absence of cilia. In: Developmental biology. 2009 ; Vol. 330, No. 2. pp. 452-460.
@article{be3235a8056d477bbed0a98d52187dbe,
title = "Suppressor of Fused inhibits mammalian Hedgehog signaling in the absence of cilia",
abstract = "The Hedgehog (Hh) family of secreted proteins regulates mammalian development and cancer formation through Gli transcription factors, which exist in both activator and repressor forms. In vertebrates, the primary cilia play an essential role in Hh signal transduction and are required for both the activator and repressor activities of Gli proteins. In the current study, we demonstrate that mouse Suppressor of Fused (Sufu) interacts with Gli proteins and inhibits Gli activator activity in the absence of cilia. Removal of Sufu in both Smoothened (Smo) and Ift88 mutants, respectively, leads to full activation of Hh signaling, suggesting that Smo-mediated repression of Sufu, but not the inhibitory function of Sufu, requires cilia. Finally, we show that Sufu is important for proper activator/repressor ratio of Gli3 protein in mice, both in the presence and absence of cilia.",
author = "Jinping Jia and {\AA}sa Kolterud and Huiqing Zeng and Amber Hoover and Stephan Teglund and Rune Toftg{\aa}rd and Aimin Liu",
year = "2009",
month = "6",
day = "15",
doi = "10.1016/j.ydbio.2009.04.009",
language = "English (US)",
volume = "330",
pages = "452--460",
journal = "Developmental Biology",
issn = "0012-1606",
publisher = "Academic Press Inc.",
number = "2",

}

Suppressor of Fused inhibits mammalian Hedgehog signaling in the absence of cilia. / Jia, Jinping; Kolterud, Åsa; Zeng, Huiqing; Hoover, Amber; Teglund, Stephan; Toftgård, Rune; Liu, Aimin.

In: Developmental biology, Vol. 330, No. 2, 15.06.2009, p. 452-460.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Suppressor of Fused inhibits mammalian Hedgehog signaling in the absence of cilia

AU - Jia, Jinping

AU - Kolterud, Åsa

AU - Zeng, Huiqing

AU - Hoover, Amber

AU - Teglund, Stephan

AU - Toftgård, Rune

AU - Liu, Aimin

PY - 2009/6/15

Y1 - 2009/6/15

N2 - The Hedgehog (Hh) family of secreted proteins regulates mammalian development and cancer formation through Gli transcription factors, which exist in both activator and repressor forms. In vertebrates, the primary cilia play an essential role in Hh signal transduction and are required for both the activator and repressor activities of Gli proteins. In the current study, we demonstrate that mouse Suppressor of Fused (Sufu) interacts with Gli proteins and inhibits Gli activator activity in the absence of cilia. Removal of Sufu in both Smoothened (Smo) and Ift88 mutants, respectively, leads to full activation of Hh signaling, suggesting that Smo-mediated repression of Sufu, but not the inhibitory function of Sufu, requires cilia. Finally, we show that Sufu is important for proper activator/repressor ratio of Gli3 protein in mice, both in the presence and absence of cilia.

AB - The Hedgehog (Hh) family of secreted proteins regulates mammalian development and cancer formation through Gli transcription factors, which exist in both activator and repressor forms. In vertebrates, the primary cilia play an essential role in Hh signal transduction and are required for both the activator and repressor activities of Gli proteins. In the current study, we demonstrate that mouse Suppressor of Fused (Sufu) interacts with Gli proteins and inhibits Gli activator activity in the absence of cilia. Removal of Sufu in both Smoothened (Smo) and Ift88 mutants, respectively, leads to full activation of Hh signaling, suggesting that Smo-mediated repression of Sufu, but not the inhibitory function of Sufu, requires cilia. Finally, we show that Sufu is important for proper activator/repressor ratio of Gli3 protein in mice, both in the presence and absence of cilia.

UR - http://www.scopus.com/inward/record.url?scp=67349198593&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=67349198593&partnerID=8YFLogxK

U2 - 10.1016/j.ydbio.2009.04.009

DO - 10.1016/j.ydbio.2009.04.009

M3 - Article

C2 - 19371734

AN - SCOPUS:67349198593

VL - 330

SP - 452

EP - 460

JO - Developmental Biology

JF - Developmental Biology

SN - 0012-1606

IS - 2

ER -