Novel targets of Akt, p21(Cipl/WAF1), and MDM2.
The phosphatidylinositol-3-OH kinase (PI-3K)/Akt signaling pathway plays a critical role in tumorigenesis. This pathway is activated by the amplification or overexpression of HER2/neu, which occurs in 30% of human breast and ovarian cancers. The recent identification of a number of Akt substrates suggests that Akt can enhance cell proliferation and inhibit apoptosis. In this review we will discuss the theme of action of Akt in regulating the cellular localization of its substrates to control proliferation and apoptosis in light of two new identified Akt substrates, p21(Cip1/WAF1) and MDM2.
Zhou
Binhua P
BP
Department of Molecular and Cellular Oncology, Breast Cancer Basic Research Program, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030-4095, USA.
Hung
Mien-Chie
MC
D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000378:metabolism*; D006801:Humans; D009687:Nuclear Proteins; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt; D051736:Proto-Oncogene Proteins c-mdm2; D015398:Signal Transduction
C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D004791:Enzyme Inhibitors; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2; D011505:Protein-Tyrosine Kinases; C494918:AKT1 protein, human; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt