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

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

Research output: Contribution to journalArticle

84 Citations (Scopus)

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
Externally publishedYes

Fingerprint

Phosphoric Monoester Hydrolases
Cell Cycle
Neoplasm Metastasis
Liver
Genes
Cell Cycle Checkpoints
p53 Genes
Phosphatidylinositol 3-Kinases
Transcriptional Activation
DNA Damage
Colorectal Neoplasms
Neoplasms
Carcinogenesis
Apoptosis

Keywords

  • CELLCYCLE

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Cite this

Basak, S., Jacobs, S. B. R., Krieg, A., Pathak, N., Zeng, Q., Kaldis, P., ... 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

The Metastasis-Associated Gene Prl-3 Is a p53 Target Involved in Cell-Cycle Regulation. / Basak, Shashwati; Jacobs, Suzanne B.R.; Krieg, Adam; Pathak, Navneeta; Zeng, Qi; Kaldis, Philipp; Giaccia, Amato J.; Attardi, Laura D.

In: Molecular Cell, Vol. 30, No. 3, 09.05.2008, p. 303-314.

Research output: Contribution to journalArticle

Basak, S, Jacobs, SBR, Krieg, A, Pathak, N, Zeng, Q, Kaldis, P, Giaccia, AJ & Attardi, LD 2008, 'The Metastasis-Associated Gene Prl-3 Is a p53 Target Involved in Cell-Cycle Regulation', Molecular Cell, vol. 30, no. 3, pp. 303-314. https://doi.org/10.1016/j.molcel.2008.04.002
Basak, Shashwati ; Jacobs, Suzanne B.R. ; Krieg, Adam ; Pathak, Navneeta ; Zeng, Qi ; Kaldis, Philipp ; Giaccia, Amato J. ; Attardi, Laura D. / The Metastasis-Associated Gene Prl-3 Is a p53 Target Involved in Cell-Cycle Regulation. In: Molecular Cell. 2008 ; Vol. 30, No. 3. pp. 303-314.
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