Artículo

Risso, G.; Pelisch, F.; Pozzi, B.; Mammi, P.; Blaustein, M.; Colman-Lerner, A.; Srebrow, A. "Modification of Akt by SUMO conjugation regulates alternative splicing and cell cycle" (2013) Cell Cycle. 12(19):3165-3174
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Abstract:

Akt/PKB is a key signaling molecule in higher eukaryotes and a crucial protein kinase in human health and disease. Phosphorylation, acetylation, and ubiquitylation have been reported as important regulatory post-translational modifications of this kinase. We describe here that Akt is modified by SUMO conjugation, and show that lysine residues 276 and 301 are the major SUMO attachment sites within this protein. We found that phosphorylation and SUMOylation of Akt appear as independent events. However, decreasing Akt SUMOylation levels severely affects the role of this kinase as a regulator of fibronectin and Bcl-x alternative splicing. Moreover, we observed that the Akt mutant (Akt E17K) found in several human tumors displays increased levels of SUMOylation and also an enhanced capacity to regulate fibronectin splicing patterns. This splicing regulatory activity is completely abolished by decreasing Akt E17K SUMO conjugation levels. Additionally, we found that SUMOylation controls Akt regulatory function at G1/S transition during cell cycle progression. These findings reveal SUMO conjugation as a novel level of regulation for Akt activity, opening new areas of exploration related to the molecular mechanisms involved in the diverse cellular functions of this kinase. © 2013 Landes Bioscience.

Registro:

Documento: Artículo
Título:Modification of Akt by SUMO conjugation regulates alternative splicing and cell cycle
Autor:Risso, G.; Pelisch, F.; Pozzi, B.; Mammi, P.; Blaustein, M.; Colman-Lerner, A.; Srebrow, A.
Filiación:Inst. de Fisiol., Biol. Molec. y Neurociencias-Consejo Nac. de Invest. Cientificas y Tecnicas, Departamento de Fisiología, Biología Molecular y Celular, Naturales-Universidad de Buenos Aires, Buenos Aires, Argentina
Centre for Gene Regulation and Expression, College of Life Sciences, University of Dundee, Dundee, United Kingdom
Palabras clave:Akt/PKB; Alternative splicing; Cell cycle; Post-translational modification; Signal transduction; SUMO; fibronectin; protein bcl x; protein kinase B; SUMO 2 protein; SUMO protein; acetylation; alternative RNA splicing; article; cell cycle; cell cycle G1 phase; cell cycle progression; cell cycle S phase; cell function; conjugation; enzyme activity; human; protein function; protein phosphorylation; sumoylation; ubiquitination; Eukaryota; Akt/PKB; alternative splicing; cell cycle; post-translational modification; signal transduction; SUMO; Alternative Splicing; bcl-X Protein; Fibronectins; G1 Phase; HEK293 Cells; HeLa Cells; Humans; Mutagenesis, Site-Directed; Phosphorylation; Proto-Oncogene Proteins c-akt; RNA Interference; RNA, Small Interfering; S Phase; Small Ubiquitin-Related Modifier Proteins; Sumoylation
Año:2013
Volumen:12
Número:19
Página de inicio:3165
Página de fin:3174
DOI: http://dx.doi.org/10.4161/cc.26183
Título revista:Cell Cycle
Título revista abreviado:Cell Cycle
ISSN:15384101
CAS:fibronectin, 86088-83-7; protein kinase B, 148640-14-6
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_15384101_v12_n19_p3165_Risso

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Citas:

---------- APA ----------
Risso, G., Pelisch, F., Pozzi, B., Mammi, P., Blaustein, M., Colman-Lerner, A. & Srebrow, A. (2013) . Modification of Akt by SUMO conjugation regulates alternative splicing and cell cycle. Cell Cycle, 12(19), 3165-3174.
http://dx.doi.org/10.4161/cc.26183
---------- CHICAGO ----------
Risso, G., Pelisch, F., Pozzi, B., Mammi, P., Blaustein, M., Colman-Lerner, A., et al. "Modification of Akt by SUMO conjugation regulates alternative splicing and cell cycle" . Cell Cycle 12, no. 19 (2013) : 3165-3174.
http://dx.doi.org/10.4161/cc.26183
---------- MLA ----------
Risso, G., Pelisch, F., Pozzi, B., Mammi, P., Blaustein, M., Colman-Lerner, A., et al. "Modification of Akt by SUMO conjugation regulates alternative splicing and cell cycle" . Cell Cycle, vol. 12, no. 19, 2013, pp. 3165-3174.
http://dx.doi.org/10.4161/cc.26183
---------- VANCOUVER ----------
Risso, G., Pelisch, F., Pozzi, B., Mammi, P., Blaustein, M., Colman-Lerner, A., et al. Modification of Akt by SUMO conjugation regulates alternative splicing and cell cycle. Cell Cycle. 2013;12(19):3165-3174.
http://dx.doi.org/10.4161/cc.26183