NEDDBOLISM AND LIVER

Organizer: IRB Barcelona

Date: Friday 09 July 2021, 12.00h

Title:"Neddbolism and Liver"

Host: Manuel Serrano, PhD.  -  Aging & Metabolism Programme - IRB Barcelona

Biomed Webinar

Abstract:

The importance of a crosstalk between transcriptional, posttranscriptional and posttranslational regulation in the wide spectrum of signaling pathways is a cutting edge research topic that has only recently been suggested in liver disease. An improved understanding of how changes in protein homeostasis can drive pathogenesis in human diseases has provided the basis for the discovery of several important therapies. The regulation of protein degradation is an essential aspect of cell signaling. Alterations in the transcriptome provide means to buffer rapid shifts in extra- or intra-cellular signals, but post-translational modifications (PTM)of the proteome provide a faster mechanism for activation or inhibition of signaling pathways and metabolism.

Neddylation is clearly emerging as an important regulator of several pathways managing metabolism, differentiation, and survival. However, despite the importance of this PTM in cell biology, the mechanisms through which neddylation controls protein propertiesas well as how its activity is controlling are still a matter of debate. Neddylation seems to be involved in cellular stress signaling, by providing a regulatory mechanism that acts like a “switch”, allowing the activation of alternative pathways dictating the key steps of the cellular stress response.

In the Liver Disease Lab in CIC bioGUNE, we attempt to challenge and expand the current view by hypothesizing that neddylation plays a fundamental role in the regulation of key pathways in response to cellular metabolic stress like starvation, calorie restriction, the excessive consumption of calories, aging and alterations in circadian rhythm . We propose that abnormal neddylation of target proteins in liver could lead to metabolic dysfunctions that are determinant for obesity and its associated pathologies, type 2 diabetes and Non Alcoholic Fatty Liver disease. Here, we also provide evidences supporting a directional relationship between Neddylation, circadian system and pathogenic processes.

This novel action will provide new avenues for understanding the mechanisms implicated in obesity development and associated metabolic alterations.

RESTRICTED to IRB Barcelona Community members