PMID- 28035348
OWN - NLM
STAT- MEDLINE
DCOM- 20170427
LR  - 20181113
IS  - 1791-2423 (Electronic)
IS  - 1019-6439 (Print)
IS  - 1019-6439 (Linking)
VI  - 50
IP  - 2
DP  - 2017 Feb
TI  - Nek2A/SuFu feedback loop regulates Gli-mediated Hedgehog signaling pathway.
PG  - 373-380
LID - 10.3892/ijo.2016.3819 [doi]
AB  - Suppressor of Fused (SuFu), one of the most conserved components of the Hedgehog 
      (Hh) signaling, binds Gli transcription factors and impedes activation of target 
      gene expression in mammalian cells. Despite the central importance of SuFu in the 
      Hh pathway, little is known about SuFu regulation. In a previous study, we 
      identified NIMA-related expressed kinase 2A (Nek2A) as a SuFu-interacting 
      protein. Here, we show that Nek2A stabilizes SuFu through impairing 
      ubiquitin/proteasome degradation of SuFu. In addition, Nek2A negatively regulates 
      target genes of Hh signaling as well as Gli2 transcriptional activity. In turn, 
      inhibition of Hh signaling by GANT61 diminishes mRNA and protein levels of Nek2A, 
      and Hh agonist promotes transcription of NEK2A gene. Chromatin 
      immunoprecipitation assays revealed that Gli1 and Gli2 directly bind to the 
      promoter regions of NEK2A gene and induced its transcription. Thus, we uncovered 
      one of the mechanisms by which Nek2A acts as a modulator of the Hh signaling 
      pathway in the context of a novel negative-feedback loop, which may offer new 
      insights into Gli-mediated Hh signaling regulation in development and human 
      diseases.
FAU - Zhou, Fen
AU  - Zhou F
AD  - Center for Experimental Medicine, The First Affiliated Hospital of Nanchang 
      University, Nanchang, Jiangxi 330006, P.R. China.
FAU - Huang, Dengliang
AU  - Huang D
AD  - Center for Experimental Medicine, The First Affiliated Hospital of Nanchang 
      University, Nanchang, Jiangxi 330006, P.R. China.
FAU - Li, Yong
AU  - Li Y
AD  - Center for Experimental Medicine, The First Affiliated Hospital of Nanchang 
      University, Nanchang, Jiangxi 330006, P.R. China.
FAU - Hu, Guanghui
AU  - Hu G
AD  - Center for Experimental Medicine, The First Affiliated Hospital of Nanchang 
      University, Nanchang, Jiangxi 330006, P.R. China.
FAU - Rao, Hai
AU  - Rao H
AD  - Department of Molecular Medicine, University of Texas Health Science Center, San 
      Antonio, TX 78229, USA.
FAU - Lu, Quqin
AU  - Lu Q
AD  - Department of Biostatistics and Epidemiology, School of Public Health, Nanchang 
      University, Nanchang, Jiangxi 330006, P.R. China.
FAU - Luo, Shiwen
AU  - Luo S
AD  - Center for Experimental Medicine, The First Affiliated Hospital of Nanchang 
      University, Nanchang, Jiangxi 330006, P.R. China.
FAU - Wang, Yao
AU  - Wang Y
AD  - Center for Experimental Medicine, The First Affiliated Hospital of Nanchang 
      University, Nanchang, Jiangxi 330006, P.R. China.
LA  - eng
PT  - Journal Article
DEP - 20161223
PL  - Greece
TA  - Int J Oncol
JT  - International journal of oncology
JID - 9306042
RN  - 0 (GLI1 protein, human)
RN  - 0 (Hedgehog Proteins)
RN  - 0 (Repressor Proteins)
RN  - 0 (SUFU protein, human)
RN  - 0 (Zinc Finger Protein GLI1)
RN  - EC 2.7.11.1 (NEK2 protein, human)
RN  - EC 2.7.11.1 (NIMA-Related Kinases)
SB  - IM
MH  - Blotting, Western
MH  - Chromatin Immunoprecipitation
MH  - Feedback, Physiological/physiology
MH  - Gene Expression Regulation/physiology
MH  - HEK293 Cells
MH  - Hedgehog Proteins/*metabolism
MH  - Humans
MH  - NIMA-Related Kinases/*metabolism
MH  - Real-Time Polymerase Chain Reaction
MH  - Repressor Proteins/*metabolism
MH  - Signal Transduction/*physiology
MH  - Transfection
MH  - Zinc Finger Protein GLI1/*metabolism
PMC - PMC5238777
EDAT- 2016/12/31 06:00
MHDA- 2017/04/28 06:00
PMCR- 2016/12/23
CRDT- 2016/12/31 06:00
PHST- 2016/10/21 00:00 [received]
PHST- 2016/12/09 00:00 [accepted]
PHST- 2016/12/31 06:00 [pubmed]
PHST- 2017/04/28 06:00 [medline]
PHST- 2016/12/31 06:00 [entrez]
PHST- 2016/12/23 00:00 [pmc-release]
AID - ijo-50-02-0373 [pii]
AID - 10.3892/ijo.2016.3819 [doi]
PST - ppublish
SO  - Int J Oncol. 2017 Feb;50(2):373-380. doi: 10.3892/ijo.2016.3819. Epub 2016 Dec 
      23.