PMC

Phosphorylation by AKT regulates compartmentalization of multiple substrates involved in cell cycle progression and inhibition of apoptosis. (A) In serum-starved cells, the pro-apoptotic transcription factors of the forkhead family and cell cycle inhibitors p21 and p27 localize in the nucleus, whereas the oncoprotein Mdm2 is restrained in the cytoplasm. (B) After growth factor (GF) stimulation and phosphorylation by AKT, the subcellular localization of these AKT substrates is diametrically changed, contributing to cell cycle progression and inhibition of apoptosis. Cytoplasmic p21 can bind to the apoptosis signal-regulating kinase (ASK1), inhibiting apoptosis. In the absence of p19/p14^ARF induction, the Mdm2-p53 complex shuttles into the cytoplasm where p53 is ubiquitinated (Ub) and targeted for degradation.