PTEN: life as a tumor suppressor.
PTEN, a tumor suppressor located at chromosome 10q23, is mutated in a variety of sporadic cancers and in two autosomal dominant hamartoma syndromes. PTEN is a phosphatase which dephosphorylates phosphatidylinositol (3,4,5)-triphosphate (PtdIns-3,4,5-P3), an important intracellular second messenger, lowering its level within the cell. By dephosphorylating PtdIns-3,4,5-P3, PTEN 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 necessary for the activation of Akt, a serine/threonine kinase involved in cell growth and survival. By blocking the activation of Akt, PTEN regulates cellular processes such as cell cycling, translation, and apoptosis. In this review, we will discuss the identification of PTEN, its mutational status in cancer, its role as a regulator of PI3K, and its domain structure.
Institute of Cancer Genetics, College of Physicians and Surgeons, Columbia University, 1150 St. Nicholas Avenue, Russ Berrie Pavilion Room 302, New York, New York 10032, USA.
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D000818:Animals; D017209:Apoptosis; D002453:Cell Cycle; D002879:Chromosomes, Human, Pair 10; D005544:Forecasting; D016147:Genes, Tumor Suppressor; D006223:Hamartoma Syndrome, Multiple / Q000235:genetics*; D006801:Humans; D019656:Loss of Heterozygosity; D051379:Mice; D009369:Neoplasms / Q000235:genetics / Q000473:pathology; D051059:PTEN Phosphohydrolase; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010744:Phosphoric Monoester Hydrolases / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D017434:Protein Structure, Tertiary; D017027:Protein Tyrosine Phosphatases / Q000378:metabolism; D015398:Signal Transduction; D025521:Tumor Suppressor Proteins
D025521:Tumor Suppressor Proteins; D019869:Phosphatidylinositol 3-Kinases; D010744:Phosphoric Monoester Hydrolases; D017027:Protein Tyrosine Phosphatases; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human