The mechanism of full activation of tumor suppressor PTEN at the phosphoinositide-enriched membrane.

ABSTRACT: Tumor suppressor PTEN, the second most highly mutated protein in cancer, dephosphorylates signaling lipid PIP₃ produced by PI3Ks. Excess PIP₃ promotes cell proliferation. The mechanism at the membrane of this pivotal phosphatase is unknown hindering drug discovery. Exploiting explicit solvent simulations, we tracked full-length PTEN trafficking from the cytosol to the membrane. We observed its interaction with membranes composed of zwitterionic phosphatidylcholine, anionic phosphatidylserine, and phosphoinositides, including signaling lipids PIP₂ and PIP₃. We tracked its moving away from the zwitterionic and getting absorbed onto anionic membrane that harbors PIP₃. We followed it localizing on microdomains enriched in signaling lipids,

SUBMITTER: Jang H 

PROVIDER: S-EPMC8169795 | biostudies-literature | 2021 May

REPOSITORIES: biostudies-literature