Regulation of the tumor suppressor PTEN by SUMO

• Published in: Cell death & disease Vol. 3; no. 9; p. e393
• Main Authors: González-Santamaría, J, Campagna, M, Ortega-Molina, A, Marcos-Villar, L, de la Cruz-Herrera, C F, González, D, Gallego, P, Lopitz-Otsoa, F, Esteban, M, Rodríguez, M S, Serrano, M, Rivas, C
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01-09-2012; Springer Nature B.V; Nature Publishing Group
• Subjects: 631/250/255/2514; 631/45/612/645; 631/80/458; 692/699/67/581; Animals; Antibodies; Biochemistry; Biomedical and Life Sciences; Cell Biology; Cell Culture; Cell Line; HEK293 Cells; Humans; Immunology; Life Sciences; MCF-7 Cells; Mice; Original; original-article; Proteasome Endopeptidase Complex - chemistry; Proteasome Endopeptidase Complex - metabolism; PTEN Phosphohydrolase - genetics; PTEN Phosphohydrolase - metabolism; Recombinant Proteins - genetics; Recombinant Proteins - metabolism; Small Ubiquitin-Related Modifier Proteins - metabolism; SUMO-1 Protein - metabolism; Sumoylation; Ubiquitination; Vesiculovirus - physiology; PTEN; VSV; SUMO
• ISSN: 2041-4889; 2041-4889
• DOI: 10.1038/cddis.2012.135

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.