Please use this identifier to cite or link to this item: https://doi.org/10.1158/1535-7163.MCT-12-0920
Title: PI3K stimulates DNA synthesis and cell-cycle progression via its p55PIK regulatory subunit interaction with PCNA
Authors: Wang, G.
Cao, X.
Lai, S.
Luo, X.
Feng, Y.
Xia, X.
Yen, P.M. 
Gong, J.
Hu, J.
Issue Date: Oct-2013
Citation: Wang, G., Cao, X., Lai, S., Luo, X., Feng, Y., Xia, X., Yen, P.M., Gong, J., Hu, J. (2013-10). PI3K stimulates DNA synthesis and cell-cycle progression via its p55PIK regulatory subunit interaction with PCNA. Molecular Cancer Therapeutics 12 (10) : 2100-2109. ScholarBank@NUS Repository. https://doi.org/10.1158/1535-7163.MCT-12-0920
Abstract: Previously, we have shown that p55PIK, an isoform of class IA phosphoinositide 3-kinase (PI3K), specifically interacts with important cell-cycle regulators, such as retinoblastoma (Rb), to promote cellcycle progression. Here, we used the glutathione S-transferase pull-down assay to identify other p55PIKinteracting 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 d (Pold) 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. © 2013 AACR.
Source Title: Molecular Cancer Therapeutics
URI: http://scholarbank.nus.edu.sg/handle/10635/126532
ISSN: 15357163
DOI: 10.1158/1535-7163.MCT-12-0920
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