PMID- 24018050
OWN - NLM
STAT- MEDLINE
DCOM- 20141203
LR  - 20211203
IS  - 1873-3913 (Electronic)
IS  - 0898-6568 (Linking)
VI  - 25
IP  - 12
DP  - 2013 Dec
TI  - RIO kinase 3 acts as a SUFU-dependent positive regulator of Hedgehog signaling.
PG  - 2668-75
LID - S0898-6568(13)00274-X [pii]
LID - 10.1016/j.cellsig.2013.08.037 [doi]
AB  - Suppressor of fused (SUFU) is an essential negative regulator of the mammalian 
      Hedgehog (HH) signaling pathway and its loss is associated with cancer 
      development. On a cellular level, endogenous SUFU can mainly be detected in the 
      cytoplasm and the nucleus. However, immunostaining of pancreatic cancer specimen 
      revealed the existence of cell types showing selective enrichment of endogenous 
      SUFU in the nucleus. Following up on this observation, we found that a SUFU 
      construct which was experimentally tethered exclusively to the nucleus was unable 
      to antagonize endogenous HH signaling, in contrast to control SUFU. These data 
      suggest that alterations in the normal subcellular distribution of SUFU might 
      interfere with its established negative role on the HH pathway. Performing a 
      multi-well kinase screen in human cells identified RIO kinase 3 (RIOK3) as a 
      novel modulator of SUFU subcellular distribution. Functionally, RIOK3 acts as a 
      SUFU-dependent positive regulator of HH signaling. Taken together, we propose 
      that factors modulating the nucleo-cytoplasmic distribution of SUFU impact on the 
      normal function of this tumor suppressing protein.
CI  - (c) 2013.
FAU - Tariki, Melanie
AU  - Tariki M
AD  - Philipps University, Institute of Molecular Biology and Tumor Research (IMT), 
      Emil-Mannkopff-Str. 2, 35037 Marburg, Germany.
FAU - Wieczorek, Sarah Alexandra
AU  - Wieczorek SA
FAU - Schneider, Philipp
AU  - Schneider P
FAU - Banfer, Sebastian
AU  - Banfer S
FAU - Veitinger, Sophie
AU  - Veitinger S
FAU - Jacob, Ralf
AU  - Jacob R
FAU - Fendrich, Volker
AU  - Fendrich V
FAU - Lauth, Matthias
AU  - Lauth M
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20130907
PL  - England
TA  - Cell Signal
JT  - Cellular signalling
JID - 8904683
RN  - 0 (Hedgehog Proteins)
RN  - 0 (Repressor Proteins)
RN  - 0 (SUFU protein, human)
RN  - EC 2.7.11.1 (Protein Serine-Threonine Kinases)
RN  - EC 2.7.11.1 (RIO kinase 3, human)
SB  - IM
MH  - Animals
MH  - COS Cells
MH  - Cell Nucleolus/metabolism
MH  - Chlorocebus aethiops
MH  - HEK293 Cells
MH  - Hedgehog Proteins/*metabolism
MH  - Humans
MH  - Mice
MH  - NIH 3T3 Cells
MH  - Protein Serine-Threonine Kinases/*metabolism
MH  - Repressor Proteins/analysis/*metabolism
MH  - *Signal Transduction
OTO - NOTNLM
OT  - GLI
OT  - GLI1
OT  - HH
OT  - Hedgehog
OT  - RIOK3
OT  - SHH
OT  - SUFU
OT  - Signal transduction
OT  - glioma-associated oncogene 1
OT  - hedgehog
OT  - right open reading frame kinase 3
OT  - sonic hedgehog
OT  - suppressor of fused
EDAT- 2013/09/11 06:00
MHDA- 2014/12/15 06:00
CRDT- 2013/09/11 06:00
PHST- 2013/08/20 00:00 [received]
PHST- 2013/08/30 00:00 [accepted]
PHST- 2013/09/11 06:00 [entrez]
PHST- 2013/09/11 06:00 [pubmed]
PHST- 2014/12/15 06:00 [medline]
AID - S0898-6568(13)00274-X [pii]
AID - 10.1016/j.cellsig.2013.08.037 [doi]
PST - ppublish
SO  - Cell Signal. 2013 Dec;25(12):2668-75. doi: 10.1016/j.cellsig.2013.08.037. Epub 
      2013 Sep 7.