Philip Cole

Mechanistic Insights into PTEN Regulation

PTEN is a PIP3 (phosphtatidyl inositol triphosphate) phosphatase and a well-established tumor suppressor gene.  PTEN is itself phosphorylated on a cluster of four C-terminal Ser/Thr residues, and this appears to negatively influence PTEN’s membrane binding activity in cells.  We will describe our efforts involving protein semisynthesis to characterize the detailed functions of these Ser/Thr phosphorylations on PTEN’s structure and function.  In addition, we will discuss aspects of how PTEN is targeted for destruction by a ubiquitin E3 ligase, WWP2, and several layers of regulation of this process.  Various aspects of our findings may point to new therapeutic directions to re-activate PTEN in cancer.