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2017 ; 37
(3
): ä Nephropedia Template TP
gab.com Text
Twit Text FOAVip
Twit Text #
English Wikipedia
Suppressor of Fused Chaperones Gli Proteins To Generate Transcriptional Responses
to Sonic Hedgehog Signaling
#MMPMID27849569
Zhang Z
; Shen L
; Law K
; Zhang Z
; Liu X
; Hua H
; Li S
; Huang H
; Yue S
; Hui CC
; Cheng SY
Mol Cell Biol
2017[Feb]; 37
(3
): ä PMID27849569
show ga
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.
|*Signal Transduction
[MESH]
|*Transcription, Genetic
[MESH]
|Active Transport, Cell Nucleus
[MESH]
|Binding Sites
[MESH]
|Cell Nucleus/metabolism
[MESH]
|Chromatin/metabolism
[MESH]
|Cilia/metabolism
[MESH]
|Cyclic AMP-Dependent Protein Kinases/metabolism
[MESH]
|Exportin 1 Protein
[MESH]
|Fibroblasts/metabolism
[MESH]
|Glycogen Synthase Kinase 3/metabolism
[MESH]
|HEK293 Cells
[MESH]
|Hedgehog Proteins/*metabolism
[MESH]
|Humans
[MESH]
|Karyopherins/metabolism
[MESH]
|Kinetics
[MESH]
|Models, Biological
[MESH]
|Molecular Chaperones/*metabolism
[MESH]
|Neural Tube/metabolism
[MESH]
|Nuclear Export Signals
[MESH]
|Phosphorylation
[MESH]
|Promoter Regions, Genetic/genetics
[MESH]
|Protein Binding
[MESH]
|Protein Transport
[MESH]
|Receptors, Cytoplasmic and Nuclear/metabolism
[MESH]
free
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