INVESTIGADORES
COLMAN LERNER Alejandro Ariel
artículos
Título:
Modification of Akt by SUMO conjugation regulates alternative splicing and cell cycle
Autor/es:
GUILLERMO RISSO; FEDERICO PELISCH; BERTA POZZI; PABLO MAMMI; MAT√ćAS BLAUSTEIN; ALEJANDRO COLMAN LERNER; ANABELLA SREBROW
Revista:
CELL CYCLE
Editorial:
LANDES BIOSCIENCE
Referencias:
Lugar: Austin, Texas; Año: 2013 vol. 12 p. 1 - 12
ISSN:
1538-4101
Resumen:
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 affect 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.