PMID- 20883817
OWN - NLM
STAT- MEDLINE
DCOM- 20110401
LR  - 20211020
IS  - 1878-5875 (Electronic)
IS  - 1357-2725 (Linking)
VI  - 42
IP  - 12
DP  - 2010 Dec
TI  - Inositol hexakisphosphate kinases promote autophagy.
PG  - 2065-71
LID - 10.1016/j.biocel.2010.09.013 [doi]
AB  - We and other authors have previously reported that increasing cellular 
      diphosphoinositol pentakisphosphate (InsP(7)) levels increases cell sensitivity 
      to cell death. In the present study, we elucidated the relationship between 
      inositol hexakisphosphate kinases (InsP(6)Ks), which form InsP(7), and autophagy 
      using InsP(6)Ks overexpression and disruption systems. A large number of 
      autophagosomes were induced in cells transfected with InsP(6)Ks, as revealed by 
      the conversion of LC3-I to LC3-II, which was examined using immunoblotting, 
      immunocytochemistry, and immuno-electron microscopy for LC3; consequently, the 
      rate of cell death was higher among these cells than among cells transfected with 
      a control vector, as shown using propidium iodide staining. However, the 
      reduction of InsP(6)Ks levels using RNAi suppressed the formation of 
      autophagosomes. Moreover, the number of autophagosomes and the rate of cell death 
      were significantly higher among cells transfected with InsP(6)Ks subjected to 
      staurosporine-induced stress than among cells transfected with InsP(6)Ks 
      subjected to normal conditions. The cell death induced by InsP(6)Ks was not 
      completely suppressed by z-VAD-fmk, a pan-caspase inhibitor. The phosphorylation 
      of mammalian target of rapamycin (mTOR) was also depressed in cells 
      overexpressing InsP(6)Ks, suggesting that the mTOR pathway regulates 
      autophagosomes generated by InsP(6)Ks. These findings imply that InsP(6)Ks 
      promote autophagy and induce caspase-independent cell death. This phenomenon 
      opens a new pathway of autophagy via InsP(6)Ks.
CI  - Copyright (c) 2010 Elsevier Ltd. All rights reserved.
FAU - Nagata, Eiichiro
AU  - Nagata E
AD  - Department of Neurology, Tokai University School of Medicine, 143 Shimo-Kasuya, 
      Isehara, Kanagawa 259-1193, Japan.
FAU - Saiardi, Adolfo
AU  - Saiardi A
FAU - Tsukamoto, Hideo
AU  - Tsukamoto H
FAU - Satoh, Tadayuki
AU  - Satoh T
FAU - Itoh, Yoshiko
AU  - Itoh Y
FAU - Itoh, Johbu
AU  - Itoh J
FAU - Shibata, Mamoru
AU  - Shibata M
FAU - Takizawa, Shunya
AU  - Takizawa S
FAU - Takagi, Shigeharu
AU  - Takagi S
LA  - eng
GR  - MC_U122680443/MRC_/Medical Research Council/United Kingdom
PT  - Journal Article
DEP - 20100929
PL  - Netherlands
TA  - Int J Biochem Cell Biol
JT  - The international journal of biochemistry & cell biology
JID - 9508482
RN  - 0 (Inositol Phosphates)
RN  - EC 2.7.4.- (Phosphotransferases (Phosphate Group Acceptor))
RN  - EC 2.7.4.21 (inositol hexakisphosphate kinase)
SB  - IM
MH  - Autophagy/*physiology
MH  - Cell Death/physiology
MH  - Cell Survival
MH  - HEK293 Cells
MH  - HeLa Cells
MH  - Humans
MH  - Immunohistochemistry
MH  - Inositol Phosphates/metabolism
MH  - Phosphorylation
MH  - Phosphotransferases (Phosphate Group Acceptor)/genetics/*metabolism
MH  - Transfection
EDAT- 2010/10/05 06:00
MHDA- 2011/04/02 06:00
CRDT- 2010/10/02 06:00
PHST- 2010/08/04 00:00 [received]
PHST- 2010/08/31 00:00 [revised]
PHST- 2010/09/20 00:00 [accepted]
PHST- 2010/10/02 06:00 [entrez]
PHST- 2010/10/05 06:00 [pubmed]
PHST- 2011/04/02 06:00 [medline]
AID - S1357-2725(10)00332-8 [pii]
AID - 10.1016/j.biocel.2010.09.013 [doi]
PST - ppublish
SO  - Int J Biochem Cell Biol. 2010 Dec;42(12):2065-71. doi: 
      10.1016/j.biocel.2010.09.013. Epub 2010 Sep 29.