Impact of p85? Alterations in Cancer.

ABSTRACT: The phosphatidylinositol 3-kinase (PI3K) pathway plays a central role in the regulation of cell signaling, proliferation, survival, migration and vesicle trafficking in normal cells and is frequently deregulated in many cancers. The p85? protein is the most characterized regulatory subunit of the class IA PI3Ks, best known for its regulation of the p110-PI3K catalytic subunit. In this review, we will discuss the impact of p85? mutations or alterations in expression levels on the proteins p85? is known to bind and regulate. We will focus on alterations within the N-terminal half of p85? that primarily regulate Rab5 and some members of the Rho-family of GTPases, as well as those that regulate PTEN (phosphatase and tensin homologue deleted on chromosome 10), the enzyme that directly counteracts PI3K signaling. We highlight recent data, mapping the interaction surfaces of the PTEN?p85? breakpoint cluster region homology (BH) domain, which sheds new light on key residues in both proteins. As a multifunctional protein that binds and regulates many different proteins, p85? mutations at different sites have different impacts in cancer and would necessarily require distinct treatment strategies to be effective.

SUBMITTER: Marshall JDS 

PROVIDER: S-EPMC6359268 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature