Disease relevance of PPP2R2B

• Spinocerebellar ataxia 12 (SCA12) is an autosomal dominant cerebellar ataxia (ADCA) described in a single family with a CAG repeat expansion in the PPP2R2B gene [1].
• Spinocerebellar ataxia type 12 (SCA12) is an autosomal dominant cerebellar ataxia associated with the expansion of an unstable CAG repeat in the 5' region of the PPP2R2B gene on chromosome 5q31-5q32 [2].
• Recombinant PP2A heterotrimers were purified from insect cells infected with baculoviruses expressing A and C, in combination with viruses expressing B alpha/PR55 alpha, B beta/PR55 beta, or SV40 small tumor antigen (st) [3].
• Whereas a PR55 beta transcript of about 2.3 kb was detected at high levels in the neuroblastoma derived cell line LA-N-1, the level of the mRNA was very low in the other human cell lines analyzed [4].
• RESULTS: SCA-12 typically presented in the 4th decade of life with action tremor of the head or arms (present in 10/10 of the affected individuals) [5].

Psychiatry related information on PPP2R2B

• Subtle parkinsonian features (9/10) and dementia (2/10) were observed in later stages of SCA-12, and psychiatric symptoms, including depression, anxiety, or delusions, were present in some affected family members (4/10) [5].

High impact information on PPP2R2B

• Expansion of a novel CAG trinucleotide repeat in the 5' region of PPP2R2B is associated with SCA12 [6].
• Since SV40 small t and the regulatory 55 kDa subunit (PR55) of protein phosphatase 2A (PP2A), have been shown to inhibit the enzyme activity of PP2A, the PR55 beta subunit could be the putative 'small t-like' factor [7].
• In accordance with this hypothesis, we show that the PR55 beta subunit is highly expressed in del-11 but not in diploid cells and is able to trans-activate the HPV16 LCR in diploid cells [7].
• SCA12 is a rare locus for autosomal dominant cerebellar ataxia: a study of an Indian family [1].
• We analyzed 77 Indian families with autosomal dominant cerebellar ataxia phenotype and confirmed the diagnosis of SCA12 in 5 families, which included a total of 6 patients and 21 family members [8].

Biological context of PPP2R2B

• Interestingly, all the affected families belong to an endogamous population, which originated in the state of Haryana, India. We identified four novel SNPs and a dinucleotide marker spanning approximately 137 kb downstream of CAG repeat in the PPP2R2B gene [2].
• 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 [9].
• Comparison of the human PR55 amino acid sequences with the data obtained from the rabbit skeletal muscle protein and a partial rabbit PR55 beta cDNA clone indicated a high degree of conservation [4].
• RAPD-based SCAR marker SCA 12 linked to recessive gene conferring resistance to anthracnose in sorghum [Sorghum bicolor (L.) Moench] [10].

Other interactions of PPP2R2B

• The putative protein shares 81 and 85% identity with B1alpha (PPP2R2A) and B1beta (PPP2R2B), respectively, and was named PPP2R2C for its high level of homology to the other two isoforms [11].
• CAG repeat polymorphisms in KCNN3 (HSKCa3) and PPP2R2B show no association or linkage to schizophrenia [12].
• 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 [9].
• However, we did not detect expansion in the SCA6, SCA8 and SCA12 loci in any patient [13].
• Analysis of SCA8 and SCA12 loci in 134 Italian ataxic patients negative for SCA1-3, 6 and 7 CAG expansions [14].

Analytical, diagnostic and therapeutic context of PPP2R2B

• Polymorphism of trinucleotide repeats in non-translated regions of SCA8 and SCA12 genes: allele distribution in a Polish control group [15].
• Detection of large pathogenic expansions in FRDA1, SCA10, and SCA12 genes using a simple fluorescent repeat-primed PCR assay [16].

References