PMID- 21979951
OWN - NLM
STAT- MEDLINE
DCOM- 20120221
LR  - 20220330
IS  - 1083-351X (Electronic)
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 286
IP  - 49
DP  - 2011 Dec 9
TI  - Akt2 kinase suppresses glyceraldehyde-3-phosphate dehydrogenase (GAPDH)-mediated 
      apoptosis in ovarian cancer cells via phosphorylating GAPDH at threonine 237 and 
      decreasing its nuclear translocation.
PG  - 42211-42220
LID - S0021-9258(20)87111-7 [pii]
LID - 10.1074/jbc.M111.296905 [doi]
AB  - Protein kinase B (Akt) plays important roles in regulation of cell growth and 
      survival, but while many aspects of its mechanism of action are known, there are 
      potentially additional regulatory events that remain to be discovered. Here we 
      detected a 36-kDa protein that was co-immunoprecipitated with protein kinase Bbeta 
      (Akt2) in OVCAR-3 ovarian cancer cells. The protein was identified to be 
      glyceraldehyde-3-phosphate dehydrogenase (GAPDH) by MALDI-TOF/TOF MS, and the 
      interaction of Akt2 and GAPDH was verified by reverse immunoprecipitation. Our 
      further study showed that Akt2 may suppress GAPDH-mediated apoptosis in ovarian 
      cancer cells. Overexpression of GAPDH increased ovarian cancer cell apoptosis 
      induced by H(2)O(2), which was inhibited by Akt2 overexpression and restored by 
      the PI3K/Akt inhibitor wortmannin or Akt2 siRNA. Akt2 phosphorylated Thr-237 of 
      GAPDH and decreased its nuclear translocation, an essential step for 
      GAPDH-mediated apoptosis. The interaction between Akt2 and GAPDH may be important 
      in ovarian cancer as immunohistochemical analysis of 10 normal and 30 cancerous 
      ovarian tissues revealed that decreased nuclear expression of GAPDH correlated 
      with activation (phosphorylation) of Akt2. In conclusion, our study suggests that 
      activated Akt2 may increase ovarian cancer cell survival via inhibition of 
      GAPDH-induced apoptosis. This effect of Akt2 is partly mediated by its 
      phosphorylation of GAPDH at Thr-237, which results in the inhibition of GAPDH 
      nuclear translocation.
FAU - Huang, Qiaojia
AU  - Huang Q
AD  - Department of Experimental Medicine, Fuzhou General Hospital (Dongfang Hospital), 
      156 North Xi-er Huan Road, Fuzhou City, Fujian Province 350025, China. Electronic 
      address: huangqj100@126.com.
FAU - Lan, Fenghua
AU  - Lan F
AD  - Department of Experimental Medicine, Fuzhou General Hospital (Dongfang Hospital), 
      156 North Xi-er Huan Road, Fuzhou City, Fujian Province 350025, China.
FAU - Zheng, Zhiyong
AU  - Zheng Z
AD  - Department of Pathology, Fuzhou General Hospital (Dongfang Hospital), 156 North 
      Xi-er Huan Road, Fuzhou City, Fujian Province 350025, China.
FAU - Xie, Feilai
AU  - Xie F
AD  - Department of Pathology, Fuzhou General Hospital (Dongfang Hospital), 156 North 
      Xi-er Huan Road, Fuzhou City, Fujian Province 350025, China.
FAU - Han, Junyong
AU  - Han J
AD  - Department of Experimental Medicine, Fuzhou General Hospital (Dongfang Hospital), 
      156 North Xi-er Huan Road, Fuzhou City, Fujian Province 350025, China.
FAU - Dong, Lihong
AU  - Dong L
AD  - Department of Experimental Medicine, Fuzhou General Hospital (Dongfang Hospital), 
      156 North Xi-er Huan Road, Fuzhou City, Fujian Province 350025, China.
FAU - Xie, Yanchuan
AU  - Xie Y
AD  - Department of Experimental Medicine, Fuzhou General Hospital (Dongfang Hospital), 
      156 North Xi-er Huan Road, Fuzhou City, Fujian Province 350025, China.
FAU - Zheng, Feng
AU  - Zheng F
AD  - Department of Nephrology, Fuzhou General Hospital (Dongfang Hospital), 156 North 
      Xi-er Huan Road, Fuzhou City, Fujian Province 350025, China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20111006
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - EC 1.2.1.- (Glyceraldehyde-3-Phosphate Dehydrogenases)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
SB  - IM
MH  - Active Transport, Cell Nucleus
MH  - Amino Acid Sequence
MH  - Apoptosis
MH  - Cell Line, Tumor
MH  - Cell Survival
MH  - Cytoplasm/metabolism
MH  - Female
MH  - Glyceraldehyde-3-Phosphate Dehydrogenases/*metabolism
MH  - Humans
MH  - Models, Molecular
MH  - Molecular Sequence Data
MH  - Mutagenesis, Site-Directed
MH  - Ovarian Neoplasms/metabolism
MH  - Phosphorylation
MH  - Proto-Oncogene Proteins c-akt/*metabolism
MH  - RNA Interference
PMC - PMC3234938
EDAT- 2011/10/08 06:00
MHDA- 2012/02/22 06:00
PMCR- 2012/12/09
CRDT- 2011/10/08 06:00
PHST- 2011/10/08 06:00 [entrez]
PHST- 2011/10/08 06:00 [pubmed]
PHST- 2012/02/22 06:00 [medline]
PHST- 2012/12/09 00:00 [pmc-release]
AID - S0021-9258(20)87111-7 [pii]
AID - M111.296905 [pii]
AID - 10.1074/jbc.M111.296905 [doi]
PST - ppublish
SO  - J Biol Chem. 2011 Dec 9;286(49):42211-42220. doi: 10.1074/jbc.M111.296905. Epub 
      2011 Oct 6.