Monday 20 June 2005
PP2A is one of the few serine/threonine-specific phosphatases in the cell. Its complex structure and regulation guarantees its many different functions.
Mutations of the PPP2R1B gene, which encodes the Abeta scaffolding subunit of serine/threonine protein phosphatase 2A (PP2A), have been identified in several types of cancer including lung and breast carcinoma.
somatic mutations in
- pulmonary carcinomas
- parathyroid adenomas
- mammary carcinomas
One of these mutations results in an alteration of glycine 90 to aspartic acid (G90D), which has been found in both tumor and genomic DNA, raising the possibility that it is associated with an increased risk for cancer.
The frequency of the G90D polymorphism in breast cancer patients is significantly higher in cases (3%) than in controls (0.3%).
The wild-type Abeta subunit interacted with the B56gamma (PPP2R5C), PR72 (PPP2R3A), and PR48 subunits of PP2A but did not interact with the B55alpha (PPP2R2A), B56alpha (PPP2R5A), or B56beta (PPP2R5B) regulatory subunits in an in vitro binding assay.
The G90D alteration inhibited the interaction of Abeta with the B56gamma subunit but had no effect on binding to the PR72 subunit.
The G90D alteration of the Abeta subunit of PP2A is associated with a low frequency of breast carcinoma and that the role of this alteration in transformation is likely to involve decreased interaction with the B56gamma regulatory subunit.
Esplin ED, Ramos P, Martinez B, Tomlinson GE, Mumby MC, Evans GA. The glycine 90 to aspartate alteration in the Abeta subunit of PP2A (PPP2R1B) associates with breast cancer and causes a deficit in protein function. Genes Chromosomes Cancer. 2006 Feb;45(2):182-90. PMID: #16276521#
Janssens V, Goris J, Van Hoof C. PP2A: the expected tumor suppressor. Curr Opin Genet Dev. 2005 Feb;15(1):34-41. PMID: #15661531#