title: Regulation of the tumor suppressor PTEN by SUMO.
abstract: The crucial function of the PTEN tumor suppressor in multiple cellular processes suggests that its activity must be tightly controlled. Both, membrane association and a variety of post-translational modifications, such as acetylation, phosphorylation, and mono- and polyubiquitination, have been reported to regulate PTEN activity. Here, we demonstrated that PTEN is also post-translationally modified by the small ubiquitin-like proteins, small ubiquitin-related modifier 1 (SUMO1) and SUMO2. We identified lysine residue 266 and the major monoubiquitination site 289, both located within the C2 domain required for PTEN membrane association, as SUMO acceptors in PTEN. We demonstrated the existence of a crosstalk between PTEN SUMOylation and ubiquitination, with PTEN-SUMO1 showing a reduced capacity to form covalent interactions with monoubiquitin and accumulation of PTEN-SUMO2 conjugates after inhibition of the proteasome. Moreover, we found that virus infection induces PTEN SUMOylation and favors PTEN localization at the cell membrane. Finally, we demonstrated that SUMOylation contributes to the control of virus infection by PTEN.
authors.affiliation: Centro Nacional de Biotecnología, CSIC, Campus Universidad Autónoma de Madrid, 28049 Madrid, Spain.
authors.forename: J
authors.initials: J
authors.lastname: González-Santamaría
authors.forename: M
authors.initials: M
authors.lastname: Campagna
authors.forename: A
authors.initials: A
authors.lastname: Ortega-Molina
authors.forename: L
authors.initials: L
authors.lastname: Marcos-Villar
authors.forename: C F
authors.initials: CF
authors.lastname: de la Cruz-Herrera
authors.forename: D
authors.initials: D
authors.lastname: González
authors.forename: P
authors.initials: P
authors.lastname: Gallego
authors.forename: F
authors.initials: F
authors.lastname: Lopitz-Otsoa
authors.forename: M
authors.initials: M
authors.lastname: Esteban
authors.forename: M S
authors.initials: MS
authors.lastname: Rodríguez
authors.forename: M
authors.initials: M
authors.lastname: Serrano
authors.forename: C
authors.initials: C
authors.lastname: Rivas
mesh_terms: D000818:Animals; D002460:Cell Line; D057809:HEK293 Cells; D006801:Humans; D061986:MCF-7 Cells; D051379:Mice; D051059:PTEN Phosphohydrolase / Q000235:genetics / Q000378:metabolism*; D046988:Proteasome Endopeptidase Complex / Q000737:chemistry / Q000378:metabolism; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D025842:SUMO-1 Protein / Q000378:metabolism*; D025841:Small Ubiquitin-Related Modifier Proteins / Q000378:metabolism*; D058207:Sumoylation; D054875:Ubiquitination; D018116:Vesiculovirus / Q000502:physiology
chemical_list: D011994:Recombinant Proteins; D025842:SUMO-1 Protein; C117909:SUMO2 protein, human; D025841:Small Ubiquitin-Related Modifier Proteins; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human; D046988:Proteasome Endopeptidase Complex