Rapid Detection of Dynamic PTEN Regulation in Living Cells Using Intramolecular BRET.

Tumor suppressor PTEN phosphatase acts to inhibit the PI3K/AKT pathway and thus regulates cell proliferation, survival, and migration. Dysregulation of PTEN function is observed in a wide range of cancers. In addition to alterations of the PTEN gene, repression of PTEN function can also occur at the protein level through changes in PTEN conformation, localization, activity, and stability.

A biosensor to monitor dynamic regulation and function of tumour suppressor PTEN in living cells.

Tumour suppressor PTEN is a phosphatase that negatively regulates the PI3K/AKT pathway. The ability to directly monitor PTEN conformation and function in a rapid, sensitive manner is a key step towards developing anti-cancer drugs aimed at enhancing or restoring PTEN-dependent pathways. Here we developed an intramolecular bioluminescence resonance energy transfer (BRET)-based biosensor, capable of detecting signal-dependent PTEN conformational changes in live cells.