Modification of Akt by SUMO conjugation regulates alternative splicing and cell cycle

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 SUM...

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Autores principales:	Risso, G., Pelisch, F., Pozzi, B., Mammi, P., Blaustein, M., Colman-Lerner, A., Srebrow, A.
Formato:	JOUR
Materias:	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 alternative splicing post-translational modification signal transduction 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
Acceso en línea:	http://hdl.handle.net/20.500.12110/paper_15384101_v12_n19_p3165_Risso
Aporte de:	Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) de Universidad de Buenos Aires

id	todo:paper_15384101_v12_n19_p3165_Risso
record_format	dspace
spelling	todo:paper_15384101_v12_n19_p3165_Risso2023-10-03T16:21:56Z Modification of Akt by SUMO conjugation regulates alternative splicing and cell cycle Risso, G. Pelisch, F. Pozzi, B. Mammi, P. Blaustein, M. Colman-Lerner, A. Srebrow, A. 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 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. JOUR info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by/2.5/ar http://hdl.handle.net/20.500.12110/paper_15384101_v12_n19_p3165_Risso
institution	Universidad de Buenos Aires
institution_str	I-28
repository_str	R-134
collection	Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA)
topic	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
spellingShingle	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 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
topic_facet	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
description	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.
format	JOUR
author	Risso, G. Pelisch, F. Pozzi, B. Mammi, P. Blaustein, M. Colman-Lerner, A. Srebrow, A.
author_facet	Risso, G. Pelisch, F. Pozzi, B. Mammi, P. Blaustein, M. Colman-Lerner, A. Srebrow, A.
author_sort	Risso, G.
title	Modification of Akt by SUMO conjugation regulates alternative splicing and cell cycle
title_short	Modification of Akt by SUMO conjugation regulates alternative splicing and cell cycle
title_full	Modification of Akt by SUMO conjugation regulates alternative splicing and cell cycle
title_fullStr	Modification of Akt by SUMO conjugation regulates alternative splicing and cell cycle
title_full_unstemmed	Modification of Akt by SUMO conjugation regulates alternative splicing and cell cycle
title_sort	modification of akt by sumo conjugation regulates alternative splicing and cell cycle
url	http://hdl.handle.net/20.500.12110/paper_15384101_v12_n19_p3165_Risso
work_keys_str_mv	AT rissog modificationofaktbysumoconjugationregulatesalternativesplicingandcellcycle AT pelischf modificationofaktbysumoconjugationregulatesalternativesplicingandcellcycle AT pozzib modificationofaktbysumoconjugationregulatesalternativesplicingandcellcycle AT mammip modificationofaktbysumoconjugationregulatesalternativesplicingandcellcycle AT blausteinm modificationofaktbysumoconjugationregulatesalternativesplicingandcellcycle AT colmanlernera modificationofaktbysumoconjugationregulatesalternativesplicingandcellcycle AT srebrowa modificationofaktbysumoconjugationregulatesalternativesplicingandcellcycle
_version_	1807315477325676544

Modification of Akt by SUMO conjugation regulates alternative splicing and cell cycle

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