PPP2R1B gene alterations inhibit interaction of PP2A-Abeta and PP2A-C proteins in colorectal cancers.
The chromosome region 11q is frequently deleted in colorectal cancers. The PPP2R1B tumor suppressor gene, encoding the beta isoform of the A subunit of serine/threonine-specific protein phosphatase 2A (PP2A-Abeta), located at 11q22-23, is inactivated in patients with cancer. The present study investigated whether or not PP2A-Abeta is altered in colorectal cancers. We searched for alterations of the PPP2R1B gene and interactions between PP2A-Abeta and PP2A-C proteins in 50 surgically resected colorectal cancer tissues. Missense mutations and homozygous deletions of the PPP2R1B gene were found in 4 of 50 patients (8%) and in 1 of 50 patients, respectively, with colorectal cancers. Deletions and/or point mutations within 412-601 amino acid sequences (binding regions of PP2A-C protein) of the PPP2R1B gene derived from colorectal cancer tissues inhibited co-immunoprecipitation of PP2A-Abeta and PP2A-C proteins. These finding suggested that the PPP2R1B gene functions as a tumor suppressor gene and acts as a molecular switch that becomes active in response to specific up-stream signals. Upon activation, the gene alters the activities of specific downstream target proteins for the cell cycle regulations and/or metabolism in some colorectal cancers.
Tamaki
Masato
M
First Department of Surgery, Fukui Medical University, Yoshida-gun, Fukui 910-1193, Japan.
Goi
Takanori
T
Hirono
Yasuo
Y
Katayama
Kanji
K
Yamaguchi
Akio
A
D002453:Cell Cycle; D045744:Cell Line, Tumor; D003062:Codon; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000378:metabolism*; D004247:DNA / Q000378:metabolism; D017353:Gene Deletion; D006720:Homozygote; D006801:Humans; D019656:Loss of Heterozygosity; D009154:Mutation; D020125:Mutation, Missense; D009363:Neoplasm Proteins / Q000235:genetics* / Q000502:physiology*; D010749:Phosphoprotein Phosphatases / Q000235:genetics* / Q000378:metabolism*; D017354:Point Mutation; D018807:Polymorphism, Single-Stranded Conformational; D011233:Precipitin Tests; D011485:Protein Binding; D054648:Protein Phosphatase 2; D015398:Signal Transduction; D014158:Transcription, Genetic
D003062:Codon; D009363:Neoplasm Proteins; C432785:PPP2R1B protein, human; D004247:DNA; D010749:Phosphoprotein Phosphatases; D054648:Protein Phosphatase 2