Title: The tumor suppressor PP2A Abeta regulates the RalA GTPase
Authors: Sablina, Anna
Chen, Wen
Arroyo, Jason D
Corral, Laura
Hector, Melissa
Bulmer, Sara E
DeCaprio, James A
Hahn, William C # ×
Issue Date: Jun-2007
Series Title: Cell vol:129 issue:5 pages:969-82
Abstract: 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.
ISSN: 0092-8674
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Non-KU Leuven Association publications
× corresponding author
# (joint) last author

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