PMID- 27849569
OWN - NLM
STAT- MEDLINE
DCOM- 20170630
LR  - 20231213
IS  - 1098-5549 (Electronic)
IS  - 0270-7306 (Print)
IS  - 0270-7306 (Linking)
VI  - 37
IP  - 3
DP  - 2017 Feb 1
TI  - Suppressor of Fused Chaperones Gli Proteins To Generate Transcriptional Responses 
      to Sonic Hedgehog Signaling.
LID - 10.1128/MCB.00421-16 [doi]
LID - e00421-16
AB  - Cellular responses to the graded Sonic Hedgehog (Shh) morphogenic signal are 
      orchestrated by three Gli genes that give rise to both transcription activators 
      and repressors. An essential downstream regulator of the pathway, encoded by the 
      tumor suppressor gene Suppressor of fused (Sufu), plays critical roles in the 
      production, trafficking, and function of Gli proteins, but the mechanism remains 
      controversial. Here, we show that Sufu is upregulated in active Shh responding 
      tissues and accompanies Gli activators translocating into and Gli repressors out 
      of the nucleus. Trafficking of Sufu to the primary cilium, potentiated by Gli 
      activators but not repressors, was found to be coupled to its nuclear import. We 
      have identified a nuclear export signal (NES) motif of Sufu in juxtaposition to 
      the protein kinase A (PKA) and glycogen synthase kinase 3 (GSK3) dual 
      phosphorylation sites and show that Sufu binds the chromatin with both Gli1 and 
      Gli3. Close comparison of neural tube development among individual Ptch1(-/-), 
      Sufu(-/-), and Ptch1(-/-); Sufu(-/-) double mutant embryos indicates that Sufu is 
      critical for the maximal activation of Shh signaling essential to the 
      specification of the most-ventral neurons. These data define Sufu as a novel 
      class of molecular chaperone required for every aspect of Gli regulation and 
      function.
CI  - Copyright (c) 2017 American Society for Microbiology.
FAU - Zhang, Ziyu
AU  - Zhang Z
AD  - Department of Developmental Genetics, School of Basic Medical Sciences, Nanjing 
      Medical University, Nanjing, Jiangsu, China.
FAU - Shen, Longyan
AU  - Shen L
AD  - Department of Developmental Genetics, School of Basic Medical Sciences, Nanjing 
      Medical University, Nanjing, Jiangsu, China.
FAU - Law, Kelvin
AU  - Law K
AD  - Department of Molecular Genetics, University of Toronto, Toronto, Canada.
FAU - Zhang, Zengdi
AU  - Zhang Z
AD  - Department of Developmental Genetics, School of Basic Medical Sciences, Nanjing 
      Medical University, Nanjing, Jiangsu, China.
FAU - Liu, Xiaotong
AU  - Liu X
AD  - Department of Developmental Genetics, School of Basic Medical Sciences, Nanjing 
      Medical University, Nanjing, Jiangsu, China.
FAU - Hua, Hu
AU  - Hua H
AD  - Department of Developmental Genetics, School of Basic Medical Sciences, Nanjing 
      Medical University, Nanjing, Jiangsu, China.
FAU - Li, Sanen
AU  - Li S
AD  - Department of Developmental Genetics, School of Basic Medical Sciences, Nanjing 
      Medical University, Nanjing, Jiangsu, China.
FAU - Huang, Huijie
AU  - Huang H
AD  - Department of Developmental Genetics, School of Basic Medical Sciences, Nanjing 
      Medical University, Nanjing, Jiangsu, China.
FAU - Yue, Shen
AU  - Yue S
AD  - Department of Developmental Genetics, School of Basic Medical Sciences, Nanjing 
      Medical University, Nanjing, Jiangsu, China.
FAU - Hui, Chi-Chung
AU  - Hui CC
AD  - Department of Molecular Genetics, University of Toronto, Toronto, Canada.
FAU - Cheng, Steven Y
AU  - Cheng SY
AD  - Department of Developmental Genetics, School of Basic Medical Sciences, Nanjing 
      Medical University, Nanjing, Jiangsu, China sycheng@njmu.edu.cn.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20170119
PL  - United States
TA  - Mol Cell Biol
JT  - Molecular and cellular biology
JID - 8109087
RN  - 0 (Chromatin)
RN  - 0 (Hedgehog Proteins)
RN  - 0 (Karyopherins)
RN  - 0 (Molecular Chaperones)
RN  - 0 (Nuclear Export Signals)
RN  - 0 (Receptors, Cytoplasmic and Nuclear)
RN  - 0 (Repressor Proteins)
RN  - 0 (Shh protein, mouse)
RN  - 0 (Sufu protein, mouse)
RN  - 0 (Trans-Activators)
RN  - EC 2.7.11.11 (Cyclic AMP-Dependent Protein Kinases)
RN  - EC 2.7.11.26 (Glycogen Synthase Kinase 3)
SB  - IM
MH  - Active Transport, Cell Nucleus
MH  - Binding Sites
MH  - Cell Nucleus/metabolism
MH  - Chromatin/metabolism
MH  - Cilia/metabolism
MH  - Cyclic AMP-Dependent Protein Kinases/metabolism
MH  - Fibroblasts/metabolism
MH  - Glycogen Synthase Kinase 3/metabolism
MH  - HEK293 Cells
MH  - Hedgehog Proteins/*metabolism
MH  - Humans
MH  - Karyopherins/metabolism
MH  - Kinetics
MH  - Models, Biological
MH  - Molecular Chaperones/*metabolism
MH  - Neural Tube/metabolism
MH  - Nuclear Export Signals
MH  - Phosphorylation
MH  - Promoter Regions, Genetic/genetics
MH  - Protein Binding
MH  - Protein Transport
MH  - Receptors, Cytoplasmic and Nuclear/metabolism
MH  - Repressor Proteins/chemistry/*metabolism
MH  - *Signal Transduction
MH  - Trans-Activators/*metabolism
MH  - *Transcription, Genetic
MH  - Up-Regulation
MH  - Exportin 1 Protein
PMC - PMC5247608
OTO - NOTNLM
OT  - Gli
OT  - Sonic Hedgehog
OT  - Suppressor of Fused
OT  - molecular chaperone
OT  - nucleocytoplasmic trafficking
EDAT- 2016/11/17 06:00
MHDA- 2017/07/01 06:00
PMCR- 2017/07/19
CRDT- 2016/11/17 06:00
PHST- 2016/07/19 00:00 [received]
PHST- 2016/11/04 00:00 [accepted]
PHST- 2016/11/17 06:00 [pubmed]
PHST- 2017/07/01 06:00 [medline]
PHST- 2016/11/17 06:00 [entrez]
PHST- 2017/07/19 00:00 [pmc-release]
AID - MCB.00421-16 [pii]
AID - 00421-16 [pii]
AID - 10.1128/MCB.00421-16 [doi]
PST - epublish
SO  - Mol Cell Biol. 2017 Jan 19;37(3):e00421-16. doi: 10.1128/MCB.00421-16. Print 2017 
      Feb 1.