The tumor suppressor PP2A Abeta regulates the RalA GTPase.
The serine-threonine protein phosphatase 2A (PP2A) is a heterotrimeric enzyme family that regulates numerous signaling pathways. Biallelic mutations of the structural PP2A Abeta subunit occur in several types of human tumors; however, the functional consequences of these cancer-associated PP2A Abeta mutations in cell transformation remain undefined. Here we show that ... suppression of PP2A Abeta expression permits immortalized human cells to achieve a tumorigenic state. Cancer-associated Abeta mutants fail to reverse tumorigenic phenotype induced by PP2A Abeta suppression, indicating that these mutants function as null alleles. Wild-type PP2A Abeta but not cancer-derived Abeta mutants form a complex with the small GTPase RalA. PP2A Abeta-containing complexes dephosphorylate RalA at Ser183 and Ser194, inactivating RalA and abolishing its transforming function. These observations identify PP2A Abeta as a tumor suppressor gene that transforms immortalized human cells by regulating the function of RalA.
Mesh Terms:
Alleles, Cell Line, Cell Transformation, Neoplastic, Genes, Tumor Suppressor, Humans, Lung Neoplasms, Mutation, Neoplasm Proteins, Phosphorylation, Protein Phosphatase 2, ral GTP-Binding Proteins
Alleles, Cell Line, Cell Transformation, Neoplastic, Genes, Tumor Suppressor, Humans, Lung Neoplasms, Mutation, Neoplasm Proteins, Phosphorylation, Protein Phosphatase 2, ral GTP-Binding Proteins
Cell
Date: Jun. 01, 2007
PubMed ID: 17540176
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