Centrosomal protein DZIP1 regulates hedgehog signaling by promoting cytoplasmic retention of transcription factor GLI3 and affecting ciliogenesis

Chengbing Wang, Wee Chuang Low, Aimin Liu, Baolin Wang

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

The primary cilium is required for Hedgehog signaling. So far, all known ciliogenic proteins regulate Hedgehog signaling through their role in ciliogenesis. Here we show that the mouse DZIP1 regulates Hedgehog signaling through two mechanisms. First, DZIP1 interacts with GLI3, a transcriptional regulator for Hedgehog signaling, and prevents GLI3 from entering the nucleus. Second, DZIP1 is required for ciliogenesis. We show that DZIP1 colocalizes and interacts with CEP164, a protein localizing at appendages of the mother centrioles, and IFT88, a component of the intraflagellar transport (IFT) machinery. Functionally, both CEP164 and Ninein appendage proteins fail to localize to ciliary appendages in Dzip1 mutant cells; IFT components are not recruited to the basal body of cilia. Importantly, the accumulation of GLI3 in the nucleus is independent of loss of primary cilia in Dzip1 mutant cells. Therefore, DZIP1 is the first known ciliogenic protein that regulates Hedgehog signaling through a dual mechanism and that biochemically links IFT machinery with Hedgehog pathway components.

Original languageEnglish (US)
Pages (from-to)29518-29529
Number of pages12
JournalJournal of Biological Chemistry
Volume288
Issue number41
DOIs
StatePublished - Oct 11 2013

Fingerprint

Hedgehogs
Cilia
Transcription Factors
Hedgehog Proteins
Proteins
Machinery
Basal Bodies
Centrioles

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

@article{2bc5d62422514f0e9bfe020eb930fffe,
title = "Centrosomal protein DZIP1 regulates hedgehog signaling by promoting cytoplasmic retention of transcription factor GLI3 and affecting ciliogenesis",
abstract = "The primary cilium is required for Hedgehog signaling. So far, all known ciliogenic proteins regulate Hedgehog signaling through their role in ciliogenesis. Here we show that the mouse DZIP1 regulates Hedgehog signaling through two mechanisms. First, DZIP1 interacts with GLI3, a transcriptional regulator for Hedgehog signaling, and prevents GLI3 from entering the nucleus. Second, DZIP1 is required for ciliogenesis. We show that DZIP1 colocalizes and interacts with CEP164, a protein localizing at appendages of the mother centrioles, and IFT88, a component of the intraflagellar transport (IFT) machinery. Functionally, both CEP164 and Ninein appendage proteins fail to localize to ciliary appendages in Dzip1 mutant cells; IFT components are not recruited to the basal body of cilia. Importantly, the accumulation of GLI3 in the nucleus is independent of loss of primary cilia in Dzip1 mutant cells. Therefore, DZIP1 is the first known ciliogenic protein that regulates Hedgehog signaling through a dual mechanism and that biochemically links IFT machinery with Hedgehog pathway components.",
author = "Chengbing Wang and Low, {Wee Chuang} and Aimin Liu and Baolin Wang",
year = "2013",
month = "10",
day = "11",
doi = "10.1074/jbc.M113.492066",
language = "English (US)",
volume = "288",
pages = "29518--29529",
journal = "Journal of Biological Chemistry",
issn = "0021-9258",
publisher = "American Society for Biochemistry and Molecular Biology Inc.",
number = "41",

}

Centrosomal protein DZIP1 regulates hedgehog signaling by promoting cytoplasmic retention of transcription factor GLI3 and affecting ciliogenesis. / Wang, Chengbing; Low, Wee Chuang; Liu, Aimin; Wang, Baolin.

In: Journal of Biological Chemistry, Vol. 288, No. 41, 11.10.2013, p. 29518-29529.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Centrosomal protein DZIP1 regulates hedgehog signaling by promoting cytoplasmic retention of transcription factor GLI3 and affecting ciliogenesis

AU - Wang, Chengbing

AU - Low, Wee Chuang

AU - Liu, Aimin

AU - Wang, Baolin

PY - 2013/10/11

Y1 - 2013/10/11

N2 - The primary cilium is required for Hedgehog signaling. So far, all known ciliogenic proteins regulate Hedgehog signaling through their role in ciliogenesis. Here we show that the mouse DZIP1 regulates Hedgehog signaling through two mechanisms. First, DZIP1 interacts with GLI3, a transcriptional regulator for Hedgehog signaling, and prevents GLI3 from entering the nucleus. Second, DZIP1 is required for ciliogenesis. We show that DZIP1 colocalizes and interacts with CEP164, a protein localizing at appendages of the mother centrioles, and IFT88, a component of the intraflagellar transport (IFT) machinery. Functionally, both CEP164 and Ninein appendage proteins fail to localize to ciliary appendages in Dzip1 mutant cells; IFT components are not recruited to the basal body of cilia. Importantly, the accumulation of GLI3 in the nucleus is independent of loss of primary cilia in Dzip1 mutant cells. Therefore, DZIP1 is the first known ciliogenic protein that regulates Hedgehog signaling through a dual mechanism and that biochemically links IFT machinery with Hedgehog pathway components.

AB - The primary cilium is required for Hedgehog signaling. So far, all known ciliogenic proteins regulate Hedgehog signaling through their role in ciliogenesis. Here we show that the mouse DZIP1 regulates Hedgehog signaling through two mechanisms. First, DZIP1 interacts with GLI3, a transcriptional regulator for Hedgehog signaling, and prevents GLI3 from entering the nucleus. Second, DZIP1 is required for ciliogenesis. We show that DZIP1 colocalizes and interacts with CEP164, a protein localizing at appendages of the mother centrioles, and IFT88, a component of the intraflagellar transport (IFT) machinery. Functionally, both CEP164 and Ninein appendage proteins fail to localize to ciliary appendages in Dzip1 mutant cells; IFT components are not recruited to the basal body of cilia. Importantly, the accumulation of GLI3 in the nucleus is independent of loss of primary cilia in Dzip1 mutant cells. Therefore, DZIP1 is the first known ciliogenic protein that regulates Hedgehog signaling through a dual mechanism and that biochemically links IFT machinery with Hedgehog pathway components.

UR - http://www.scopus.com/inward/record.url?scp=84885633427&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84885633427&partnerID=8YFLogxK

U2 - 10.1074/jbc.M113.492066

DO - 10.1074/jbc.M113.492066

M3 - Article

C2 - 23955340

AN - SCOPUS:84885633427

VL - 288

SP - 29518

EP - 29529

JO - Journal of Biological Chemistry

JF - Journal of Biological Chemistry

SN - 0021-9258

IS - 41

ER -