Figure 2. Mechanisms of PTEN regulation. PTEN is regulated at different levels. (A) PTEN mRNA transcription is activated by early growth response protein 1, P53, MYC, PPARγ, C-repeat binding factor 1, and others, and inhibited by NF-κB, proto-oncogene c-Jun, TGF-β, and BMI-1. (B) PTEN mRNA is also post-transcriptionally regulated by PTEN-targeting miRNAs, including miR-21, miR-17-92, and others. (C) Active site phosphorylation, ubiquitination, oxidation, acetylation, and protein-protein interactions can also regulate PTEN activity. The phosphorylation leads to a “closed” state of PTEN and maintains PTEN stability. Dephosphorylation of the C-terminal tail opens the PTEN phosphatase domain, thereby activating PTEN.