PTEN (Phosphatase and Tensin homologue deleted on chromosome 10, 10q23.3) is the dominant
phosphatase responsible for the dephosphorylation of the 3-position phosphate from the inositol ring of
phosphatidylinositol 3,4,5 triphosphate (PIP3), and thereby directly antagonizes the actions mediated by
Phosphatidylinositol-3 Kinase (PI3K). PI3K functions in numerous pathways and cellular processes, including
tumourigenesis. Therefore, mechanisms regulating PTEN function, either positively or negatively are of great
interest not only to oncogenesis but also to other aspects of human health. Since its discovery in 1997, PTEN
has been one of the most-heavily studied tumour suppressors and has been the subject of numerous reviews.
Most investigations and reviews center on PTEN’s function and its regulation. While the regulation of PTEN
function via genetic and/or epigenetic mechanisms has been extensively studied, the impact of protein-protein
interaction on PTEN function remains less clear. Recent research has revealed that PTEN can be specifically
inhibited by its interaction with other proteins, which are collectively termed PTEN-negative regulators (PTENNRs).
This review will summarize our current understanding on the protein network that influences PTEN
function with a specific focus on PTEN-NRs.