Alterations in protein phosphatase 2A subunit interaction in human carcinomas of the lung and colon with mutations in the Aβ subunit gene

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 wild-type 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 wild-type 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.