PTEN: a novel anti-oncogenic function independent of phosphatase activity.
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 approximately 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.
Okumura
Koichi
K
Ludwig Institute for Cancer Research, San Diego Branch, University of California at San Diego, La Jolla, California 92093-0660, USA.
Zhao
Mujun
M
DePinho
Ronald A
RA
Furnari
Frank B
FB
Cavenee
Webster K
WK
D000818:Animals; D002384:Catalysis; D002453:Cell Cycle; D002462:Cell Membrane / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D016147:Genes, Tumor Suppressor; D006801:Humans; D008954:Models, Biological; D009687:Nuclear Proteins / Q000737:chemistry; D051059:PTEN Phosphohydrolase / Q000737:chemistry* / Q000378:metabolism; D010744:Phosphoric Monoester Hydrolases / Q000737:chemistry / Q000378:metabolism*; D016601:RNA-Binding Proteins
C113292:MCRS1 protein, human; D009687:Nuclear Proteins; D016601:RNA-Binding Proteins; D010744:Phosphoric Monoester Hydrolases; D051059:PTEN Phosphohydrolase