PMID- 27297360
OWN - NLM
STAT- MEDLINE
DCOM- 20171128
LR  - 20221029
IS  - 1873-3913 (Electronic)
IS  - 0898-6568 (Linking)
VI  - 28
IP  - 9
DP  - 2016 Sep
TI  - Nek2A phosphorylates and stabilizes SuFu: A new strategy of Gli2/Hedgehog 
      signaling regulatory mechanism.
PG  - 1304-1313
LID - S0898-6568(16)30144-9 [pii]
LID - 10.1016/j.cellsig.2016.06.010 [doi]
AB  - Suppressor of Fused (SuFu) plays a conservative role in the regulation of the Gli 
      transcription factors within the Hedgehog (Hh) signaling pathway. Despite the 
      central importance of SuFu in the Hh pathway, little is known about its 
      regulation. Here, we performed a GAL4-based yeast two-hybrid screen using human 
      SuFu as bait, and identified NIMA-related expressed kinase 2A (Nek2A) as a new 
      SuFu-interacting protein, which was also confirmed by glutathione-S-transferase 
      pull-down and co-immunoprecipitation assays. Intriguingly, Nek2A is found to 
      stabilize SuFu at least partly depending on its kinase activity, thereby 
      triggering phosphorylation of the SuFu protein. Moreover, the phosphorylated SuFu 
      inhibits the nuclear localization and transcriptional activity of Gli2/Hh 
      signaling. These findings reveal a new mechanism of mammalian SuFu regulation, 
      and offers novel insights into Hh signaling regulation in development and human 
      disease.
CI  - Copyright (c) 2016 Elsevier Inc. All rights reserved.
FAU - Wang, Yao
AU  - Wang Y
AD  - Center for Experimental Medicine, The First Affiliated Hospital of Nanchang 
      University, Nanchang, Jiangxi 330006, China; Jiangxi Key Laboratory of Molecular 
      Diagnostics and Precision Medicine, China.
FAU - Li, Yong
AU  - Li Y
AD  - Center for Experimental Medicine, The First Affiliated Hospital of Nanchang 
      University, Nanchang, Jiangxi 330006, China.
FAU - Hu, Guanghui
AU  - Hu G
AD  - Center for Experimental Medicine, The First Affiliated Hospital of Nanchang 
      University, Nanchang, Jiangxi 330006, China; Jiangxi Key Laboratory of Molecular 
      Diagnostics and Precision Medicine, China.
FAU - Huang, Xuan
AU  - Huang X
AD  - Center for Experimental Medicine, The First Affiliated Hospital of Nanchang 
      University, Nanchang, Jiangxi 330006, China.
FAU - Rao, Hai
AU  - Rao H
AD  - Department of Molecular Medicine, University of Texas Health Science Center, San 
      Antonio, TX 78229, USA.
FAU - Xiong, Xiangyang
AU  - Xiong X
AD  - School of Medicine, Nanchang University, Nanchang, Jiangxi 330006, China.
FAU - Luo, Zhijun
AU  - Luo Z
AD  - School of Medicine, Nanchang University, Nanchang, Jiangxi 330006, China.
FAU - Lu, Quqin
AU  - Lu Q
AD  - Department of Biostatistics & Epidemiology, School of Public Health, Nanchang 
      University, Nanchang, Jiangxi 330006, China.
FAU - Luo, Shiwen
AU  - Luo S
AD  - Center for Experimental Medicine, The First Affiliated Hospital of Nanchang 
      University, Nanchang, Jiangxi 330006, China; Jiangxi Key Laboratory of Molecular 
      Diagnostics and Precision Medicine, China. Electronic address: 
      shiwenluo@ncu.edu.cn.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20160611
PL  - England
TA  - Cell Signal
JT  - Cellular signalling
JID - 8904683
RN  - 0 (GLI2 protein, human)
RN  - 0 (Hedgehog Proteins)
RN  - 0 (Nuclear Proteins)
RN  - 0 (Repressor Proteins)
RN  - 0 (SUFU protein, human)
RN  - 0 (Zinc Finger Protein Gli2)
RN  - EC 2.7.11.1 (NEK2 protein, human)
RN  - EC 2.7.11.1 (NIMA-Related Kinases)
SB  - IM
MH  - Amino Acid Sequence
MH  - Animals
MH  - Cell Line
MH  - Hedgehog Proteins/*metabolism
MH  - Humans
MH  - Mice
MH  - NIMA-Related Kinases/*metabolism
MH  - Nuclear Proteins/*metabolism
MH  - Phosphorylation
MH  - Protein Binding
MH  - Protein Interaction Domains and Motifs
MH  - Protein Interaction Mapping
MH  - Protein Stability
MH  - Repressor Proteins/chemistry/*metabolism
MH  - *Signal Transduction
MH  - Zinc Finger Protein Gli2/*metabolism
OTO - NOTNLM
OT  - Hedgehog signaling pathway
OT  - NIMA-related expressed kinase 2A
OT  - Phosphorylation
OT  - Suppressor of fused
OT  - Transcription factor Gli2
EDAT- 2016/06/15 06:00
MHDA- 2017/11/29 06:00
CRDT- 2016/06/15 06:00
PHST- 2016/01/05 00:00 [received]
PHST- 2016/05/31 00:00 [revised]
PHST- 2016/06/09 00:00 [accepted]
PHST- 2016/06/15 06:00 [entrez]
PHST- 2016/06/15 06:00 [pubmed]
PHST- 2017/11/29 06:00 [medline]
AID - S0898-6568(16)30144-9 [pii]
AID - 10.1016/j.cellsig.2016.06.010 [doi]
PST - ppublish
SO  - Cell Signal. 2016 Sep;28(9):1304-1313. doi: 10.1016/j.cellsig.2016.06.010. Epub 
      2016 Jun 11.