@article{d816b7682b0d4c0fb6f824ef6ac11b67,
title = "PTEN: A novel anti-oncogenic function independent of phosphatase activity",
abstract = "The PTEN gene is an important tumor suppressor mutated in a number of cancers. To date, its growth regulatory properties have been intimately linked to its ability to act as a protein and phosphoinositol phosphatase. Inactivation of the enzymatic activity of PTEN is primarily due to direct mutation of its amino-terminal catalytic domain but ∼20% of mutations are in the carboxy-terminus, which regulates membrane localization, protein stability, cellular migration and p53 function. We identified a novel protein that interacts with this domain, the v-jun transcriptional target, MSP58. Binding of MSP58 to PTEN results in the suppression of MSP58-mediated transformation. However, this PTEN effect does not require its catalytic activity, suggesting additional mechanisms of PTEN action.",
keywords = "C2 domain, FHA domain, GLTSCR2/PICT1, MSP58, PDZ, PTEN",
author = "Koichi Okumura and Mujun Zhao and DePinho, {Ronald A.} and Furnari, {Frank B.} and Cavenee, {Webster K.}",
note = "Funding Information: A clue that this might not be the entire story is that ~20% of all known PTEN mutations We gratefully acknowledge discussions especially in tumors are located within the carboxy-terminus,6 suggesting that this region may also Institute and Michelle Mendoza of the Biomedicalwith Dr. Robert Bachoo of the Dana-Farber Cancer have biological functions distinct from those mediated by the catalytic domain. The Sciences Graduate Program of UCSD as well as carboxy-terminal domain of PTEN is phosphorylated in vivo, regulating its stability and with Drs. Elizabeth Maher, Cameron Brennan, activity.7The physiologically relevant function of PTEN phosphorylation, other than Lynda Chin, David Louis and David Rowitch of control of protein stability and translocation, is ambiguous and the C2 domain contributes our program project consortium. This work was to these regulations by binding to the plasma membrane and properly orientating the supported in part by Scholar Awards for cancer phosphatase domain.8 PTEN protein phosphatase activity inhibits cell migration by research from the Kimmel Foundation and the V inducing a conformational change that exposes the C2-domain.9 Besides phosphatase Foundation (F.F.), grant CA95616 from the activity, the C2 domain itself can also regulate cell migration,10 as well as regulate p53 National Cancer Institute (W.C., F.F., R.D.P.) and protein stability and transcriptional activity by competing with MDM2 for direct binding.11",
year = "2005",
month = apr,
doi = "10.4161/cc.4.4.1614",
language = "English (US)",
volume = "4",
pages = "540--542",
journal = "Cell Cycle",
issn = "1538-4101",
publisher = "Landes Bioscience",
number = "4",
}