Switching Akt: from survival signaling to deadly response

被引:120
作者
Los, Marek [1 ,2 ]
Maddika, Subbareddy [3 ]
Erb, Bettina [1 ]
Schulze-Osthoff, Klaus [1 ]
机构
[1] Univ Tubingen, Interfac Inst Biochem, D-72076 Tubingen, Germany
[2] BioApplicat Enterprises, Winnipeg, MB R2V 2N6, Canada
[3] Yale Univ, Sch Med, Dept Therapeut Radiol, New Haven, CT 06520 USA
关键词
Akt; apoptosis; oncogenes; oxidative stress; senescence; TUMOR-SUPPRESSOR; C-MYC; APOPTOSIS; PATHWAY; CANCER; CELLS; INHIBITION; TRANSFORMATION; PROLIFERATION; SENESCENCE;
D O I
10.1002/bies.200900005
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Akt, a protein kinase hyperactivated in many tumors, plays a major role in both cell survival and resistance to tumor therapy. A recent study,((1)) along with other evidences, shows interestingly, that Akt is not a single-function kinase, but may facilitate rather than inhibit cell death under certain conditions. This hitherto undetected function of Akt is accomplished by its ability to increase reactive oxygen species and to suppress antioxidant enzymes. The ability of Akt to down-regulate antioxidant defenses uncovers a novel Achilles' heel, which could be exploited by oxidant therapies in order to selectively eradicate tumor cells that express high levels of Akt activity.
引用
收藏
页码:492 / 495
页数:4
相关论文
共 25 条
[1]   Nuclear Akt associates with PKC-phosphorylated Ebp1, preventing DNA fragmentation by inhibition of caspase-activated DNase [J].
Ahn, Jee-Yin ;
Liu, Xia ;
Liu, Zhixue ;
Pereira, Lorena ;
Cheng, Dongmei ;
Peng, Junmin ;
Wade, Paul A. ;
Hamburger, Anne W. ;
Ye, Keqiang .
EMBO JOURNAL, 2006, 25 (10) :2083-2095
[2]   Senescent cells, tumor suppression, and organismal aging: Good citizens, bad neighbors [J].
Campisi, J .
CELL, 2005, 120 (04) :513-522
[3]   Crucial role of p53-dependent cellular senescence in suppression of Pten-deficient tumorigenesis [J].
Chen, ZB ;
Trotman, LC ;
Shaffer, D ;
Lin, HK ;
Dotan, ZA ;
Niki, M ;
Koutcher, JA ;
Scher, HI ;
Ludwig, T ;
Gerald, W ;
Cordon-Cardo, C ;
Pandolfi, PP .
NATURE, 2005, 436 (7051) :725-730
[4]   No death without life: vital functions of apoptotic effectors [J].
Galluzzi, L. ;
Joza, N. ;
Tasdemir, E. ;
Maiuri, M. C. ;
Hengartner, M. ;
Abrams, J. M. ;
Tavernarakis, N. ;
Penninger, J. ;
Madeo, F. ;
Kroemer, G. .
CELL DEATH AND DIFFERENTIATION, 2008, 15 (07) :1113-1123
[5]   Drug discovery approaches targeting the PI3K/Akt pathway in cancer [J].
Garcia-Echeverria, C. ;
Sellers, W. R. .
ONCOGENE, 2008, 27 (41) :5511-5526
[6]   The Akt-mTOR tango and its relevance to cancer [J].
Hay, N .
CANCER CELL, 2005, 8 (03) :179-183
[7]   Only Akt1 is required for proliferation, while Akt2 promotes cell cycle exit through p21 binding [J].
Heron-Milhavet, Lisa ;
Franckhauser, Celine ;
Rana, Vanessa ;
Berthenet, Cyril ;
Fisher, Daniel ;
Hemmings, Brian A. ;
Fernandez, Anne ;
Lamb, Ned J. C. .
MOLECULAR AND CELLULAR BIOLOGY, 2006, 26 (22) :8267-8280
[8]   Connecting proliferation and apoptosis in development and disease [J].
Hipfner, DR ;
Cohen, SM .
NATURE REVIEWS MOLECULAR CELL BIOLOGY, 2004, 5 (10) :805-815
[9]  
Jänicke RU, 2007, CELL CYCLE, V6, P407
[10]   The dark side of a tumor suppressor:: anti-apoptotic p53 [J].
Janicke, R. U. ;
Sohn, D. ;
Schulze-Osthoff, K. .
CELL DEATH AND DIFFERENTIATION, 2008, 15 (06) :959-976