Protean PTEN: form and function.
Germline mutations distributed across the PTEN tumor-suppressor gene have been found to result in a wide spectrum of phenotypic features. Originally shown to be a major susceptibility gene for both Cowden syndrome (CS), which is characterized by multiple hamartomas and an increased risk of breast, thyroid, and endometrial cancers, and Bannayan-Riley-Ruvalcaba syndrome, which is characterized by lipomatosis, macrocephaly, and speckled penis, the PTEN hamartoma tumor syndrome spectrum has broadened to include Proteus syndrome and Proteus-like syndromes. Exon 5, which encodes the core motif, is a hotspot for mutations likely due to the biology of the protein. PTEN is a major lipid 3-phosphatase, which signals down the PI3 kinase/AKT pro-apoptotic pathway. Furthermore, PTEN is a protein phosphatase, with the ability to dephosphorylate both serine and threonine residues. The protein-phosphatase activity has also been shown to regulate various cell-survival pathways, such as the mitogen-activated kinase (MAPK) pathway. Although it is well established that PTEN's lipid-phosphatase activity, via the PI3K/AKT pathway, mediates growth suppression, there is accumulating evidence that the protein-phosphatase/MAPK pathway is equally important in the mediation of growth arrest and other crucial cellular functions.
Waite
Kristin A
KA
Human Cancer Genetics, Department of Molecular Virology, Immunology and Medical Genetics, The Ohio State University, 420 West 12th Avenue, Columbus, OH 43210, USA.
Eng
Charis
C
D000818:Animals; D004195:Disease Models, Animal; D018095:Germ-Line Mutation / Q000235:genetics; D006223:Hamartoma Syndrome, Multiple / Q000235:genetics / Q000378:metabolism; D006801:Humans; D051379:Mice; D051059:PTEN Phosphohydrolase; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010744:Phosphoric Monoester Hydrolases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D016715:Proteus Syndrome / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction; D013329:Structure-Activity Relationship; D025521:Tumor Suppressor Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*
D025521:Tumor Suppressor Proteins; D019869:Phosphatidylinositol 3-Kinases; D010744:Phosphoric Monoester Hydrolases; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human