title: 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.
abstract: 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 Bβ (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.
authors: 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.
authors: Qiaojia
authors: Q
authors: Huang
authors: Department of Experimental Medicine, Fuzhou General Hospital (Dongfang Hospital), 156 North Xi-er Huan Road, Fuzhou City, Fujian Province 350025, China.
authors: Fenghua
authors: F
authors: Lan
authors: Department of Pathology, Fuzhou General Hospital (Dongfang Hospital), 156 North Xi-er Huan Road, Fuzhou City, Fujian Province 350025, China.
authors: Zhiyong
authors: Z
authors: Zheng
authors: Department of Pathology, Fuzhou General Hospital (Dongfang Hospital), 156 North Xi-er Huan Road, Fuzhou City, Fujian Province 350025, China.
authors: Feilai
authors: F
authors: Xie
authors: Department of Experimental Medicine, Fuzhou General Hospital (Dongfang Hospital), 156 North Xi-er Huan Road, Fuzhou City, Fujian Province 350025, China.
authors: Junyong
authors: J
authors: Han
authors: Department of Experimental Medicine, Fuzhou General Hospital (Dongfang Hospital), 156 North Xi-er Huan Road, Fuzhou City, Fujian Province 350025, China.
authors: Lihong
authors: L
authors: Dong
authors: Department of Experimental Medicine, Fuzhou General Hospital (Dongfang Hospital), 156 North Xi-er Huan Road, Fuzhou City, Fujian Province 350025, China.
authors: Yanchuan
authors: Y
authors: Xie
authors: Department of Nephrology, Fuzhou General Hospital (Dongfang Hospital), 156 North Xi-er Huan Road, Fuzhou City, Fujian Province 350025, China.
authors: Feng
authors: F
authors: Zheng
mesh_terms: D021581:Active Transport, Cell Nucleus; D000595:Amino Acid Sequence; D017209:Apoptosis; D045744:Cell Line, Tumor; D002470:Cell Survival; D003593:Cytoplasm / Q000378:metabolism; D005260:Female; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases / Q000378:metabolism*; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D010051:Ovarian Neoplasms / Q000378:metabolism; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D034622:RNA Interference
chemical_list: D005987:Glyceraldehyde-3-Phosphate Dehydrogenases; D051057:Proto-Oncogene Proteins c-akt