PI3K stimulates DNA synthesis and cell-cycle progression via its p55PIK regulatory subunit interaction with PCNA.

Published

Journal Article

Previously, we have shown that p55PIK, an isoform of class I(A) phosphoinositide 3-kinase (PI3K), specifically interacts with important cell-cycle regulators, such as retinoblastoma (Rb), to promote cell-cycle progression. Here, we used the glutathione S-transferase pull-down assay to identify other p55PIK-interacting proteins besides Rb in a Rb-deficient cell line and found that p55PIK interacted with proliferation cell nuclear antigen (PCNA), which plays a key role in coordinating both initiation of the leading strand DNA replication and discontinuous lagging strand synthesis. Overexpression of p55PIK increased, and knockdown decreased, DNA synthesis and DNA replication by modulating the binding of DNA polymerase δ (Polδ) to PCNA. Moreover, a cell-permeable peptide containing the N-terminal-binding domain of p55PIK (TAT-N24) disrupted the p55PIK-PCNA interaction in cancer cells, and also inhibited the DNA synthesis and tumor growth in cell culture and in vivo. Altogether, our results show that the p55PIK-PCNA interaction is important in regulating DNA synthesis and contributes to tumorigenesis. Furthermore, the p55PIK-PCNA interaction provides a potential new target for anticancer drug development.

Full Text

Duke Authors

Cited Authors

  • Wang, G; Cao, X; Lai, S; Luo, X; Feng, Y; Xia, X; Yen, PM; Gong, J; Hu, J

Published Date

  • October 2013

Published In

Volume / Issue

  • 12 / 10

Start / End Page

  • 2100 - 2109

PubMed ID

  • 23939377

Pubmed Central ID

  • 23939377

Electronic International Standard Serial Number (EISSN)

  • 1538-8514

Digital Object Identifier (DOI)

  • 10.1158/1535-7163.MCT-12-0920

Language

  • eng

Conference Location

  • United States