5519

PPP2R1B

PP2A-Abeta|PR65B;protein phosphatase 2, regulatory subunit A, beta;PPP2R1B;protein phosphatase 2, regulatory subunit A, beta

PP2A, subunit A, PR65-beta isoform|PP2A, subunit A, R1-beta isoform|protein phosphatase 2 (formerly 2A), regulatory subunit A, beta isoform|protein phosphatase 2, structural/regulatory subunit A, beta|serine/threonine-protein phosphatase 2A 65 kDa regulat

11q23.2

protein-coding

Protein phosphatase 2A (PP2A) holoenzyme plays a critical role in cell cycle control and growth factor signaling. The PPP2R1B gene encodes the beta isoforms of the subunit A of the PP2A. We aimed to evaluate the role of the PPP2R1B gene in the pathogenesis of cervical cancer. Twenty-four women with primary cervical cancer were included. All resected specimens were divided into two groups: (1) cervical cancers (n = 24), (2) nearby noncancerous tissues (n = 24). We performed nested reverse transcriptase-polymerase chain reaction analysis and complementary DNA sequencing on the genomic DNA samples of all specimens. The aberrant transcripts and gene mutation as well as the genotype and allele frequencies of codon 66 CTA/CTG of PPP2R1B genes in both groups were compared. The percentages of aberrant transcripts between both groups were nonsignificantly different (20.8% vs 33.3%). There was no mutation in all specimens. The genotype and allele frequencies between both groups were non-different. Proportions of CTA homozygote/heterozygote/CTG homozygote were (1) 66.7/8.3/25% and (2) 58.3/12.5/29.2%. Proportions of CTA/CTG alleles in both groups were (1) 70.8/29.2% and (2) 64.6/35.4%. We conclude that PPP2R1B genes may not play a role in the carcinogenesis of cervical cancer. mutations of PPP2R1B gene are not frequent in cervical cancer.

The serine-threonine protein phosphatase 2A (PP2A) is a heterotrimeric enzyme family that regulates numerous signaling pathways. Biallelic mutations of the structural PP2A Abeta subunit occur in several types of human tumors; however, the functional consequences of these cancer-associated PP2A Abeta mutations in cell transformation remain undefined. Here we show that suppression of PP2A Abeta expression permits immortalized human cells to achieve a tumorigenic state. cancer-associated Abeta mutants fail to reverse tumorigenic phenotype induced by PP2A Abeta suppression, indicating that these mutants function as null alleles. Wild-type PP2A Abeta but not cancer-derived Abeta mutants form a complex with the small GTPase RalA. PP2A Abeta-containing complexes dephosphorylate RalA at Ser183 and Ser194, inactivating RalA and abolishing its transforming function. These observations identify PP2A Abeta as a tumor suppressor gene that transforms immortalized human cells by regulating the function of RalA.