| First Author | Basak S | Year | 2008 |
| Journal | Mol Cell | Volume | 30 |
| Issue | 3 | Pages | 303-14 |
| PubMed ID | 18471976 | Mgi Jnum | J:136964 |
| Mgi Id | MGI:3797439 | Doi | 10.1016/j.molcel.2008.04.002 |
| Citation | Basak S, et al. (2008) The metastasis-associated gene Prl-3 is a p53 target involved in cell-cycle regulation. Mol Cell 30(3):303-14 |
| abstractText | 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(1) 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. |
