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

Oncogene volume 20, pages 1892–1899 (2001)Cite this article

Abstract

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, Aα and Aβ. Here we report about the properties of eight Aβ 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 andB′′/PR72. Of three mutants that behaved like the wild-type Aβ 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 Aα and Aβ 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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Acknowledgements

We thank Glen Evans for the Aβ cDNA plasmid, Marc Mumby for the Bα and B′α1 cDNA plasmids, and Brian Hemmings for the B′′/PR72 cDNA plasmid. We also acknowledge the UCSD Cancer Center Sequencing Facility. This work was supported by the Tobacco-Related Diseases Research Program, grant 8RT-0037, and Public Health Service grant CA-36111.

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  1. Department of Pathology, University of California at San Diego, La Jolla, California, 92093, CA, USA

    Ralf Ruediger, Huong T Pham & Gernot Walter

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Ruediger, R., Pham, H. & Walter, G. Alterations in protein phosphatase 2A subunit interaction in human carcinomas of the lung and colon with mutations in the Aβ subunit gene. Oncogene 20, 1892–1899 (2001). https://doi.org/10.1038/sj.onc.1204279

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