PTEN (gene)

PTEN, also known as phosphatase and tensin homolog, is a human gene that encodes a protein with phosphatase activity. The PTEN protein functions as a tumor suppressor by regulating cell growth, cell proliferation, apoptosis, and cell migration. It achieves this primarily through its ability to dephosphorylate phosphoinositide (3,4,5)-trisphosphate (PIP3), a key signaling molecule in the PI3K/AKT/mTOR pathway.

Located on chromosome 10q23.31, PTEN is one of the most frequently mutated or deleted tumor suppressor genes in human cancers. Mutations in PTEN have been implicated in a wide range of cancers, including prostate, breast, glioblastoma, endometrial, and melanoma. These mutations often lead to loss of PTEN function, resulting in increased levels of PIP3, overactivation of the PI3K/AKT/mTOR pathway, and uncontrolled cell growth.

Beyond cancer, germline mutations in PTEN are also associated with several inherited disorders, including Cowden syndrome, Bannayan-Riley-Ruvalcaba syndrome, and Proteus syndrome. These syndromes are characterized by an increased risk of developing certain cancers and benign tumors, as well as developmental abnormalities.

The PTEN protein is a dual-specificity phosphatase, meaning it can remove phosphate groups from both phosphotyrosine and phosphoserine/threonine residues on its target proteins. While its lipid phosphatase activity towards PIP3 is the best-characterized function, PTEN also has protein phosphatase activity and regulates other signaling pathways independent of the PI3K/AKT/mTOR pathway.

Regulation of PTEN activity is complex and involves multiple mechanisms, including phosphorylation, ubiquitination, oxidation, and interactions with other proteins. Understanding the mechanisms that regulate PTEN function and the consequences of PTEN loss is crucial for developing effective cancer therapies and for managing the inherited disorders associated with PTEN mutations.