Parkin: a novel function in cellular plasticity - ubiquitination of nuclear targets and its impact on tissue repair

• Grant number: 23/01903-6
• Support Opportunities: Regular Research Grants
• Start date: December 01, 2023
• End date: November 30, 2025
• Field of knowledge: Biological Sciences - Morphology - Histology
• Principal Investigator: Igor Luchini Baptista
• Grantee: Igor Luchini Baptista
• Host Institution: Faculdade de Ciências Aplicadas (FCA). Universidade Estadual de Campinas (UNICAMP). Limeira , SP, Brazil
• Associated researchers: Adriana Souza Torsoni ; Augusto Ducati Luchessi ; Fernando Moreira Simabuco

Abstract

The different tissues and organs of mammals have regenerative competence, differing in capacity and extent, as well as signaling or dependence on specific cells. In general, the tissue regenerative process involves the resumption of tissue functionality as well as three-dimensional reorganization of cells and extracellular matrix. In this way, investigating how satellite cells act in muscle regeneration, as well as how hepatocytes maintain their functionality during liver repair, are crucial to understand different cellular processes under the demand of tissue reorganization. The ubiquitination of transcription factors is crucial for the regulation of several target genes, regardless of tissue or cell. In general, ubiquitinations in amino acids lysine at position 48 (K48) and lysine 63 (K63) are the most studied, the first being related to the degradation of the target protein by the 26S proteasome system and the second related to changes in the activity of the target protein. Parkin, an E3 ubiquitin ligase, has the ability to ubiquitinate cytoplasmic and mitochondrial targets at two positions, K48 and K63. We recently described the location of Parkin in the nucleus of muscle progenitor cells and we have observed, in an ongoing project, the presence of Parkin in the nucleus of hepatocytes. However, it is unclear what functions Parkin may play, as well as whether this nuclear localization impacts the expression of genes related to the repair of both tissues. Thus, the aim of the current proposal is to investigate the effects of Parkin nuclear localization in muscle and liver progenitor cells during the tissue repair process, as well as a molecular investigation of the role of nuclear Parkin on the levels of ubiquitination of specific targets in a cell-like manner. We intend to elucidate new interactions of Parkin with proteins targeting its ubiquitination, and the impact of such post-translational modifications on the expression of genes involved in the differentiation of these cells. (AU)