Depletion of PKD1 by an antisense oligodeoxynucleotide induces premature G1/S-phase transition.
Autosomal dominant polycystic kidney disease (ADPKD) is characterized by the growth of epithelial cells and the influx of cyst fluid. The 14-kb mRNA of the polycystic kidney disease gene, PKD1, encodes the polycystin-1 protein, whose function remains unknown. In this study, we observed that polycystin-1 localized in epithelial cell-cell contacts of 293 cells. We found, by bromodeoxyuridine (BrdU) incorporation experiments and Western blot analysis of S-phase-specific cyclins, that the depletion of polycystin-1 led to an increased cell proliferation rate and caused a premature G1/S-phase transition. In addition, we showed that the depletion of polycystin-1 reduced the amount of p53 in 293 cells irradiated by UV light, suggesting that polycystin-1 acts as a regulator of G1 checkpoint, which controls entry into the S phase and prevents the replication of damaged DNA. Our results might provide an insight into the formation and progression of ADPKD cysts.
Kim
Hyunho
H
Graduate School of Biotechnology, Korea University, Seoul 136-701, Korea.
Bae
Yoonhee
Y
Jeong
Woocho
W
Ahn
Curie
C
Kang
Seongman
S
D000595:Amino Acid Sequence; D001483:Base Sequence; D015153:Blotting, Western; D001973:Bromodeoxyuridine; D002448:Cell Adhesion / Q000528:radiation effects; D049109:Cell Proliferation / Q000528:radiation effects*; D002478:Cells, Cultured; D004249:DNA Damage / Q000528:radiation effects; D004261:DNA Replication; D004847:Epithelial Cells / Q000378:metabolism / Q000473:pathology / Q000528:radiation effects; D016193:G1 Phase / Q000502:physiology* / Q000528:radiation effects; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D020319:Oligodeoxyribonucleotides, Antisense / Q000494:pharmacology*; D016891:Polycystic Kidney, Autosomal Dominant / Q000235:genetics / Q000378:metabolism; D011506:Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D016196:S Phase / Q000502:physiology* / Q000528:radiation effects; D050396:TRPP Cation Channels; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D014466:Ultraviolet Rays
D001973:Bromodeoxyuridine; D020319:Oligodeoxyribonucleotides, Antisense; D011506:Proteins; D012333:RNA, Messenger; D050396:TRPP Cation Channels; D016159:Tumor Suppressor Protein p53