TY - JOUR
T1 - Depletion of PKD1 by an antisense oligodeoxynucleotide induces premature G1/S-phase transition
AU - Kim, Hyunho
AU - Bae, Yoonhee
AU - Jeong, Woocho
AU - Ahn, Curie
AU - Kang, Seongman
N1 - Funding Information:
This work was supported in part by a grant from the Ministry of Health & Welfare, Republic of Korea and by a Korea University Grant.
Copyright:
Copyright 2008 Elsevier B.V., All rights reserved.
PY - 2004/6
Y1 - 2004/6
N2 - 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.
AB - 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.
KW - ADPKD
KW - Antisense oligonucleotides
KW - PKD1
KW - p53
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U2 - 10.1038/sj.ejhg.5201136
DO - 10.1038/sj.ejhg.5201136
M3 - Article
C2 - 15054393
AN - SCOPUS:3142735085
SN - 1018-4813
VL - 12
SP - 433
EP - 440
JO - European Journal of Human Genetics
JF - European Journal of Human Genetics
IS - 6
ER -