Study of Akt relocalization and posttranslational modification dynamics: towards an Akt molecular code

MATÍAS BLAUSTEIN

Barcelona

Seminario; Seminario del Departamento de Genética; 2017

Departamento de Genética. Facultad de Biología (UB). Instituto de Biomedicina de la Universidad de Barcelona (IBUB).

At least 15% of vertebrate protein coding capability is linked to receptors, components of the signaling system and transcription regulatory proteins and its dysfunction is associated with several pathologies. In the case of cancer, changes in the function of signaling systems are so important that they are utilized to define and classify different types of tumors. We study the signaling response and cell fate of cultured human cells in response to extracellular or intracellular signals. In order to do that, we use different fluorescent reporters, which allow us to quantify the activation of signaling pathways in real-time and single cells.Particularly, Akt (also known as PKB), is a kinase involved in a great variety of processes like protein translation, cell proliferation, survival and malignant transformation. Novel Akt posttranslational modifications (PTM) have been reported in the last years. Whether there is a molecular code that transduces these modification patterns into changes in Akt subcellular localization, target specificity and function is still poorly understood. We developed a dual strategy for automated imaging and quantitative measurement of the localization profiles of Akt as well as for annotation of novel Akt substrates. Here, we report novel subcellular compartments to which Akt is recruited as well as novel Akt PTM and present an interaction network classification of the Akt substrates related to these compartments, to specific biological processes and to particular human diseases. Our data shed light towards understanding the Akt molecular code, which can lead us to understand complex cell and tumor behaviors.