Suppressor of Fused Inhibits Mammalian Hedgehog Signaling in the Absence of Cilia

Overview

Journal Dev Biol

Publisher Elsevier

Specialties Biology
Reproductive Medicine

Date 2009 Apr 18

PMID 19371734

Citations 76

Authors

Jinping Jia

Asa Kolterud

Huiqing Zeng

Amber Hoover

Stephan Teglund

Rune Toftgard

Aimin Liu

Affiliations

Soon will be listed here.

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.

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