Parkin and its role in ubiquitination of nuclear targets during liver regeneration in mice

• Grant number: 24/16418-9
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: February 01, 2025
• End date: January 31, 2029
• Field of knowledge: Biological Sciences - Morphology - Histology
• Principal Investigator: Igor Luchini Baptista
• Grantee: Ana Laura Vieira da Silva
• Host Institution: Faculdade de Ciências Aplicadas (FCA). Universidade Estadual de Campinas (UNICAMP). Limeira , SP, Brazil

Abstract

Different mammalian tissues and organs have regenerative capacities, differing in competence and extent, as well as in signaling or dependence on specific cells. In general, the regenerative process involves the resumption of tissue functionality as well as the three-dimensional reorganization of cells and the extracellular matrix. The liver is responsible for the main metabolic processes of the body, and is unique in its capacity for regeneration, which acts as a protective mechanism against the loss of liver tissue, thus allowing the organ to continue to perform its functions even after suffering significant injuries. Thus, investigating how hepatocytes maintain their functionality during liver repair is crucial for understanding the cellular processes that occur under the demand for tissue reorganization. In this regard, ubiquitination of transcriptional factors is critical for the regulation of many target genes, independent of tissue or cell. In general, ubiquitination at amino acids lysine at position 48 (K48) and lysine 63 (K63) are the most studied, the former being related to target protein degradation by the 26S proteasome system and the latter associated with changes in target protein activity. Parkin, an E3 ubiquitin ligase, can act by ubiquitinating cytoplasmic and mitochondrial targets at both positions, K48 and K63. Recently, we have observed in the current project the presence of Parkin in the nucleus of hepatocytes, however, it is unclear what functions such protein may play and whether this nuclear localization impacts the expression of genes related to tissue repair. Therefore, the current project aims to investigate the effects of Parkin nuclear localization in liver cells during the repair process. To this end, we aim to identify nuclear proteins ubiquitinated via Parkin for modification and degradation during liver regeneration.