Genomic organization and precise physical location of protein phosphatase 2A regulatory subunit A beta isoform gene on chromosome band 11q23

• Published in: Gene 1998-09, Vol.217 (1), p.107-116
• Main Authors: Baysal, Bora E., Farr, Joan E., Goss, James R., Devlin, B., Richard III, Charles W.
• Format: Article
• Language: English
• Subjects: Base Sequence; Bubble-vectorette; Chromosome Banding; Chromosome Mapping; Chromosomes, Human, Pair 11; DNA Mutational Analysis; DNA Primers; Exons; Female; Hereditary paraganglioma; Holoenzymes - genetics; Humans; Introns; Isoenzymes - genetics; Molecular Sequence Data; Organ Specificity; Paraganglioma - genetics; Phosphoprotein Phosphatases - genetics; Polymorphism, Single-Stranded Conformational; PP2A; PPP2R1B; Pregnancy; primer extension; Protein Phosphatase 2; Rapid amplification of cDNA ends; Reverse Transcriptase Polymerase Chain Reaction
• ISSN: 0378-1119; 1879-0038
• DOI: 10.1016/S0378-1119(98)00350-3

Protein phosphatase 2A (PP2A) holoenzyme plays a critical role in cell-cycle control and growth-factor signaling, and is implicated in tumorigenesis. Because the protein phosphatase 2 regulatory subunit A beta isoform gene ( PPP2R1B) maps within the critical region of hereditary paraganglioma (PGL1) on chromosomal band 11q23, we characterized its genomic structure and evaluated it as a candidate gene for PGL1. PPP2R1B has 15 exons spanning approx. 27 kb genomic distance. We placed the exons on genomic EcoRI fragments and identified their flanking intronic sequences. The gene was oriented from telomere to centromere. Splice acceptor and donor sites of all introns conformed to the GT/AG rule. Northern analysis with a cDNA probe identified 2.5 kb and 5.0 kb transcript sizes. We identified an ATG initiation codon in a favorable context and mapped two transcription start sites 15 bp and 66 bp upstream of it. We also mapped a 3′-polyadenylation site 504 bp downstream of the TGA stop codon, consistent with the 2.5 kb transcript size. We did not detect germ-line mutations by single-stranded conformational polymorphism (SSCP) analysis or major rearrangements by Southern analysis in a set of PGL1 patients. In conclusion, we precisely mapped and characterized the structure of PPP2R1B and evaluated it as a candidate gene for PGL1.