PTEN: Life as a tumor suppressor

PTEN, a tumor suppressor located at chromosome 10q23, is mutated in a varie ty of sporadic cancers and in two autosomal dominant hamartoma syndromes. P TEN is a phosphatase which dephosphorylates phosphatidylinositol (3,4,5)-tr iphosphate (PtdIns-3,4,5-P3), an important intracellular second messanger, lowering its level within the cell, By dephosphorylating PtdIns-3,4,5-P3, P TEN acts in opposition to phosphatidylinositol 3-kinase (PI3K), which has a pivotal role in the creation of PtdIns-3,4,5-P3. PtdIns-3,4,5-P3 is necess ary for the activation of Akt, a serine/threonine kinase involved in cell g rowth and survival. By blocking the activation of Akt, PTEN regulates cellu lar processes such as cell cycling, translation, and apoptosis. In this rev iew, we will discuss the identification of PTEN, its mutational status in c ancer, its role as a regulator of PI3K, and its domain structure. (C) 2001 Academic Press.