Fig. 4. Nuclear and cytoplasmic PTEN signaling. PTEN localizes to both the cytoplasm and the nucleus and shuttles between each by a variety of mechanisms. PTEN function is, at least in part, determined by its subcellular localization. The `classic' PTEN function is cytoplasmic and includes downregulation of AKT, which increases p27 levels and thereby leads to apoptosis. By contrast, nuclear PTEN has a variety of functions: downregulation of MAPK (ERK), leading to a decrease in cyclin D1 levels and G0-G1 arrest; upregulation of RAD51 levels and double-stranded-break repair; an interaction with CENP-C, which enhances centromere stability specifically and overall genomic stability; and apoptosis.