PMID- 16921268
OWN - NLM
STAT- MEDLINE
DCOM- 20070129
LR  - 20220321
IS  - 1554-8627 (Print)
IS  - 1554-8627 (Linking)
VI  - 2
IP  - 4
DP  - 2006 Oct-Dec
TI  - Elongation factor-2 kinase: its role in protein synthesis and autophagy.
PG  - 294-6
AB  - Elongation factor-2 kinase (eEF-2 kinase; Ca(2+)/calmodulin-dependent kinase III) 
      controls the rate of peptide chain elongation. The activity of eEF-2 kinase is 
      increased in many malignancies, yet its precise function in carcinogenesis 
      remains unknown. Autophagy, a well-defined survival pathway in yeast, may also 
      play an important role in oncogenesis. Furthermore, the autophagic response to 
      nutrient deprivation is regulated by the mammalian target of rapamycin (mTOR). 
      eEF-2 kinase lies downstream of mTOR and is regulated by several kinases in this 
      pathway. Therefore, we studied the role of eEF-2 kinase in autophagy. Knockdown 
      of eEF-2 kinase by RNA interference inhibited autophagy in several cell types as 
      measured by light chain 3 (LC3)-II formation, acidic vesicular organelle 
      staining, and electron microscopy. In contrast, overexpression of eEF-2 kinase 
      increased autophagy. Furthermore, inhibition of autophagy markedly decreased the 
      viability of glioblastoma cells grown under conditions of nutrient depletion. 
      These results suggest that eEF-2 kinase plays a regulatory role in the autophagic 
      process in tumor cells and may promote cancer cell survival under conditions of 
      nutrient deprivation. Therefore, eEF-2 kinase activation may be a part of a 
      survival mechanism in glioblastoma, and targeting this kinase may represent a 
      novel approach to cancer treatment.
FAU - Hait, William N
AU  - Hait WN
AD  - Department of Pharmacology, University of Medicine and Dentistry of New Jersey, 
      Robert Wood Johnson Medical School, 195 Little Albany Street, New Brunswick, New 
      Jersey 08901, USA. haitwn@umdnj.edu
FAU - Wu, Hao
AU  - Wu H
FAU - Jin, Shenkan
AU  - Jin S
FAU - Yang, Jin-Ming
AU  - Yang JM
LA  - eng
GR  - CA43888/CA/NCI NIH HHS/United States
GR  - CA72720/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20061003
PL  - United States
TA  - Autophagy
JT  - Autophagy
JID - 101265188
RN  - EC 2.7.- (Protein Kinases)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.1.17 (EEF2K protein, human)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - EC 2.7.11.17 (Calcium-Calmodulin-Dependent Protein Kinases)
RN  - EC 2.7.11.20 (Elongation Factor 2 Kinase)
SB  - IM
MH  - Animals
MH  - Autophagy/*physiology
MH  - Calcium-Calmodulin-Dependent Protein Kinases/antagonists & 
      inhibitors/genetics/*metabolism
MH  - Cell Line, Tumor
MH  - Elongation Factor 2 Kinase
MH  - Humans
MH  - Neoplasms/genetics/metabolism
MH  - Protein Biosynthesis/*physiology
MH  - Protein Kinases/metabolism
MH  - RNA Interference
MH  - TOR Serine-Threonine Kinases
EDAT- 2006/08/22 09:00
MHDA- 2007/01/30 09:00
CRDT- 2006/08/22 09:00
PHST- 2006/08/22 09:00 [pubmed]
PHST- 2007/01/30 09:00 [medline]
PHST- 2006/08/22 09:00 [entrez]
AID - 2857 [pii]
AID - 10.4161/auto.2857 [doi]
PST - ppublish
SO  - Autophagy. 2006 Oct-Dec;2(4):294-6. doi: 10.4161/auto.2857. Epub 2006 Oct 3.