title: Regulation of PTEN phosphorylation and stability by a tumor suppressor candidate protein.
abstract: The tumor suppressor PTEN plays an essential role in regulating signaling pathways involved in cell growth and apoptosis and is inactivated in a wide variety of tumors. In this study, we have identified a protein, referred to as PICT-1 (protein interacting with carboxyl terminus 1), that binds to the C terminus of PTEN and regulates its phosphorylation and turnover. Down-regulation of PICT-1 in MCF7 cells by RNA interference enhances the degradation of PTEN with a concomitant decrease in its phosphorylation. PTEN C-terminal tumor-associated mutants, which are highly susceptible to protein degradation, have lost the ability to bind to PICT-1 along with their reduced phosphorylation, suggesting that their rapid turnover results from impaired binding to PICT-1. Our results identify PICT-1 as a PTEN-interacting protein that promotes the phosphorylation and stability of PTEN. These findings suggest a novel molecular mechanism underlying the turnover of PTEN, which also provides an explanation for the loss of PTEN function due to C-terminal mutations.
authors.affiliation: Department of Pharmacology, Tokyo Metropolitan Institute of Medical Science, 3-18-22 Honkomagome, Bunkyo-ku, Tokyo 113-8613, Japan.
authors.forename: Fumiaki
authors.initials: F
authors.lastname: Okahara
authors.forename: Hideki
authors.initials: H
authors.lastname: Ikawa
authors.forename: Yasunori
authors.initials: Y
authors.lastname: Kanaho
authors.forename: Tomohiko
authors.initials: T
authors.lastname: Maehama
mesh_terms: D045744:Cell Line, Tumor; D006801:Humans; D051059:PTEN Phosphohydrolase; D010744:Phosphoric Monoester Hydrolases / Q000737:chemistry / Q000378:metabolism*; D010766:Phosphorylation; D025521:Tumor Suppressor Proteins / Q000737:chemistry / Q000378:metabolism* / Q000502:physiology*
chemical_list: D025521:Tumor Suppressor Proteins; D010744:Phosphoric Monoester Hydrolases; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human