Figure 3.

Assumption of the CAV ORF3 protein-induced apoptosis of tumor cells (Los et al., 2009). Through association with PI3-K, the ORF3 protein can lead to constitutive activation of PI3-K and the subsequent phosphorylation of Akt. The nuclear translocation of Akt activates CDK2 by direct and indirect phosphorylation, which subsequently phosphorylates the ORF3 protein at Thr108. Then, the ORF3 protein is forced to accumulate in the nucleus. In the cytoplasm, the ORF3 protein can interact with various proteins, including Nmi, Hippi, Ppil3, FADD, Bcl10, and Hsp70. In the nucleus, the ORF3 protein associates with other types of interaction partners, such as DEDAF, PML and APC. In addition, the ORF3 protein can trigger Nurr77 phosphorylation and then make its nuclear export. Nurr77 in the cytoplasm is known to regulate the Bcl-2 family such that apoptosis is induced via the mitochondrial pathway.