Journal
ONCOGENE
Volume 20, Issue 15, Pages 1892-1899Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/sj.onc.1204279
Keywords
PP2A; A beta subunit; mutation; lung and colon cancer; tumor suppressor
Funding
- NCI NIH HHS [CA-36111] Funding Source: Medline
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Protein phosphatase 2A (PP2A) consists of three subunits, A, B and C, The A and B subunits have regulatory functions while C is the catalytic subunit, PP2A core enzyme is composed of subunits A and C, and the holoenzyme of subunits A, B and C, All subunits exist as multiple isoforms or splice variants. The A subunit exists as two isoforms, A alpha and A beta. Here we report about the properties of eight A beta mutants, which were found in human lung and colon cancer. These mutants were reconstructed by site-directed mutagenesis and assayed for their ability to bind B and C subunits, Two mutants showed decreased binding of PR72, a member of the B family of B subunits, but normal C subunit binding; two mutants exhibited decreased binding of the C subunit and of B /PR72; and one mutant showed increased binding of both the C subunit and B /PR72, Of three mutants that behaved like the wildtype A beta subunit, one is a polymorphic variant and another one is altered outside the binding region for B and C subunits, Importantly, we also found that the wildtype A alpha and A beta isoforms, although 85% identical, are remarkably different in their ability to bind B and C subunits, Our findings may have important implications in regard to the role of PP2A as a tumor suppressor.
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