Human PPP2R3B ELISA Matched Antibody Pair

Spinocerebellar ataxia type 12 (SCA12) is an autosomal dominant neurodegenerative disorder which has been described in pedigrees of German American and Indian descent. The phenotype typically begins with tremor in the fourth decade, progressing to include ataxia and other cerebellar and cortical signs. SCA12 is associated with an expansion of a CAG repeat in the 5' region of the gene PPP2R2B, which encodes a brain-specific regulatory subunit of the protein phosphatase PP2A. The repeat size ranges from 55 to 78 triplets in the mutant allele of affected individuals, and from 9 to 28 triplets in normal alleles. It is possible that an expansion mutation in PPP2R2B may influence PPP2R2B expression, perhaps altering the activity of PP2A, an enzyme implicated in multiple cellular functions, including cell cycle regulation, tau phosphorylation, and apoptosis. (C) 2001 Elsevier Science Inc.

Background: The multifunctional protein phosphatase 2A (PP2A) is a heterotrimeric serine/threonine protein phosphatase composed of a scaffolding, catalytic and regulatory subunits. By modifying various downstream signal transducers, the aberrant expression of the brain-targeted regulatory subunit PPP2R2B is associated with the onset of a panel of neuronal disorders. The alternatively splicing of PPP2R2B encodes two regulatory subunit isoforms that determine cellular distribution of the neuron-specific holoenzyme to mitochondria (B beta 2) and cytoplasm (B beta 1), respectively. Results: Human neuroblastoma cells were transfected with PPP2R2B constructs encoding the complete sequences of B beta 2 and B beta 1, respectively. The colonies with antibiotic resistance were selected as stable cell lines. Both ectopic B beta 1 and B beta 2 clones exhibited characteristics of autophagy. To test how cells respond to reactive oxygen species generators, the cells were treated with either hydrogen peroxide or t-butyl hydroperoxide and B beta 2 clones induced cell death. Suppression of autophagy using either RNA interference of the essential autophagy gene or pharmacological inhibitor rescued cell death caused by oxidative stress. Conclusions: Cells with ectopically expressed mitochondria-targeted regulatory subunit PPP2R2B of the holoenzyme PP2A were shown predisposed to autophagy and oxidative stress induced cell death that is related to apoptosis. The results promised a model for studying the mechanism and function of aberrant PPP2R2B expression in neuronal cells. The work provided a new target for understanding and prevention of neuropathogenesis.