Depletion of PKD1 by an antisense oligodeoxynucleotide induces premature G1/S-phase transition

Hyunho Kim, Yoonhee Bae, Woocho Jeong, Curie Ahn, Seongman Kang

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)433-440
Number of pages8
JournalEuropean Journal of Human Genetics
Volume12
Issue number6
DOIs
Publication statusPublished - 2004 Jun

Keywords

  • ADPKD
  • Antisense oligonucleotides
  • PKD1
  • p53

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

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