期刊
CELL
卷 129, 期 5, 页码 969-982出版社
CELL PRESS
DOI: 10.1016/j.cell.2007.03.047
关键词
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资金
- NCI NIH HHS [P01 CA050661-190009, P01 CA050661, P01 CA50661] Funding Source: Medline
The serine-threonine protein phosphatase 2A (PP2A) is a heterotrimeric enzyme family that regulates numerous signaling pathways. Biallelic mutations of the structural PP2A A beta subunit occur in several types of human tumors; however, the functional consequences of these cancer-associated PP2A A beta mutations in cell transformation remain undefined. Here we show that suppression of PP2A A beta expression permits immortalized human cells to achieve a tumorigenic state. Cancer-associated A beta mutants fail to reverse tumorigenic phenotype induced by PP2A A beta suppression, indicating that these mutants function as null alleles. Wild-type PP2A A beta but not cancer-derived A beta mutants form a complex with the small GTPase RalA. PP2A A beta-containing complexes dephosphorylate RalA at Ser183 and Ser194, inactivating RalA and abolishing its transforming function. These observations identify PP2A A beta as a tumor suppressor gene that transforms immortalized human cells by regulating the function of RalA.
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