The Metastasis-Associated Gene Prl-3 Is a p53 Target Involved in Cell-Cycle Regulation

Shashwati Basak, Suzanne B.R. Jacobs, Adam J. Krieg, Navneeta Pathak, Qi Zeng, Philipp Kaldis, Amato J. Giaccia, Laura D. Attardi

Research output: Contribution to journalArticle

86 Scopus citations

Abstract

The p53 tumor suppressor restricts tumorigenesis through the transcriptional activation of target genes involved in cell-cycle arrest and apoptosis. Here, we identify Prl-3 (phosphatase of regenerating liver-3) as a p53-inducible gene. Whereas previous studies implicated Prl-3 in metastasis because of its overexpression in metastatic human colorectal cancer and its ability to promote invasiveness and motility, we demonstrate here that Prl-3 is an important cell-cycle regulator. Consistent with a role in DNA damage-induced cell-cycle arrest, Prl-3 overexpression induces G1 arrest downstream of p53 by triggering a PI3K-Akt-activated negative feedback loop. Surprisingly, attenuation of Prl-3 expression also elicits an arrest response, suggesting that basal level Prl-3 expression is pivotal for normal cell-cycle progression. Our findings highlight key dose-dependent functions of Prl-3 in both positive and negative regulation of cell-cycle progression and provide insight into Prl-3's role in cancer progression.

Original languageEnglish (US)
Pages (from-to)303-314
Number of pages12
JournalMolecular Cell
Volume30
Issue number3
DOIs
StatePublished - May 9 2008

Keywords

  • CELLCYCLE

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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    Basak, S., Jacobs, S. B. R., Krieg, A. J., Pathak, N., Zeng, Q., Kaldis, P., Giaccia, A. J., & Attardi, L. D. (2008). The Metastasis-Associated Gene Prl-3 Is a p53 Target Involved in Cell-Cycle Regulation. Molecular Cell, 30(3), 303-314. https://doi.org/10.1016/j.molcel.2008.04.002