Approaches to Investigating the Protein Interactome of PTEN

The
tumor suppressor phosphatase and tensin homologue (PTEN) is
a redox-sensitive dual specificity phosphatase with an essential role
in the negative regulation of the PI3K-AKT signaling pathway, affecting
metabolic and cell survival processes. PTEN is commonly mutated in
cancer, and dysregulation in the metabolism of PIP3 is
implicated in other diseases such as diabetes. PTEN interactors are
responsible for some functional roles of PTEN beyond the negative
regulation of the PI3K pathway and are thus of great importance in
cell biology. Both high-data content proteomics-based approaches and
low-data content PPI approaches have been used to investigate the
interactome of PTEN and elucidate further functions of PTEN. While
low-data content approaches rely on co-immunoprecipitation and Western
blotting, and as such require previously generated hypotheses, high-data
content approaches such as affinity pull-down proteomic assays or
the yeast 2-hybrid system are hypothesis generating. This review provides
an overview of the PTEN interactome, including redox effects, and
critically appraises the methods and results of high-data content
investigations into the global interactome of PTEN. The biological
significance of findings from recent studies is discussed and illustrates
the breadth of cellular functions of PTEN that can be discovered by
these approaches.