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Description

Phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN (UniProt: P60484, also known as Mutated in multiple advanced cancers 1, Phosphatase and tensin homolog, PTEN) is encoded by the PTEN (also known as MMAC1, TEP1) gene (Gene ID: 5728) in human. PTEN belongs to the family of lipid phosphatases. It contains an N-terminal phosphatase catalytic domain, a C2-domain that binds to phospholipid membranes, and a C-terminal regulatory tail. It is a dual-specific phosphatase, which dephosphorylates both lipid and protein substrates. PTEN blocks the phosphatidylinositol 3-kinase/Akt signaling pathway by removing the phosphate in the 3-position on phosphoinositide-3, 4, 5-trisphosphate (PIP3). Dephosphorylation of PIP3 is an important factor in cell growth, proliferation, apoptosis, and survival. Dephosphorylation of PIP3 blocks Akt signaling that can lead to higher activity of pro-apoptotic molecules such as Bad and Caspase-9. PTEN is considered a major tumor suppressor and its mutations are reported in several human tumors. Over seventy different types of PTEN mutation have been recorded in patients with Cowden syndrome. PTEN -/- mice exhibit higher levels of 3 -phosphorylated phospholipids and die during embryogenesis due to the failure of developmental apoptosis. Lysine 13 is one of the conserved sites for ubiquitination and monoubiquitination is essential for the movement of PTEN from cytoplasm to the nucleus. NEDD4-1 is identified as E3 ligase that induces both mono- and poly-ubiquitination of PTEN.