The metastasis-associated gene Prl-3 is a p53 target involved in cell-cycle regulation
(2008) In Molecular Cell 30(3). p.303-314- 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... (More)
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.
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- author
- Basak, Shashwati ; Jacobs, Suzanne B.R. ; Krieg, Adam J. ; Pathak, Navneeta ; Zeng, Qi ; Kaldis, Philipp LU ; Giaccia, Amato J. and Attardi, Laura D.
- publishing date
- 2008-05-09
- type
- Contribution to journal
- publication status
- published
- keywords
- CELLCYCLE
- in
- Molecular Cell
- volume
- 30
- issue
- 3
- pages
- 303 - 314
- publisher
- Cell Press
- external identifiers
-
- scopus:42949121716
- pmid:18471976
- ISSN
- 1097-2765
- DOI
- 10.1016/j.molcel.2008.04.002
- language
- English
- LU publication?
- no
- id
- b65c7eca-f16b-43c4-8749-3434e0e37e2b
- date added to LUP
- 2019-09-18 14:13:54
- date last changed
- 2024-04-30 21:50:31
@article{b65c7eca-f16b-43c4-8749-3434e0e37e2b, abstract = {{<p>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 G<sub>1</sub> 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.</p>}}, author = {{Basak, Shashwati and Jacobs, Suzanne B.R. and Krieg, Adam J. and Pathak, Navneeta and Zeng, Qi and Kaldis, Philipp and Giaccia, Amato J. and Attardi, Laura D.}}, issn = {{1097-2765}}, keywords = {{CELLCYCLE}}, language = {{eng}}, month = {{05}}, number = {{3}}, pages = {{303--314}}, publisher = {{Cell Press}}, series = {{Molecular Cell}}, title = {{The metastasis-associated gene Prl-3 is a p53 target involved in cell-cycle regulation}}, url = {{http://dx.doi.org/10.1016/j.molcel.2008.04.002}}, doi = {{10.1016/j.molcel.2008.04.002}}, volume = {{30}}, year = {{2008}}, }