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. Copyright 2002, Elsevier Science (USA). All rights reserved.