Scholarship 23/02076-6 - Regeneração muscular, Transdução de sinais - BV FAPESP
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Parkin and a new function for cellular plasticity: the ubiquitination of nuclear targets and its impact on skeletal muscle regeneration

Grant number: 23/02076-6
Support Opportunities:Scholarships in Brazil - Doctorate
Start date until: May 01, 2024
Status:Discontinued
Field of knowledge:Biological Sciences - Morphology - Histology
Principal Investigator:Igor Luchini Baptista
Grantee:Isabela Aparecida Divino
Host Institution: Faculdade de Ciências Aplicadas (FCA). Universidade Estadual de Campinas (UNICAMP). Limeira , SP, Brazil

Abstract

Mammalian tissues and organs have regenerative properties, 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 muscle tissue, investigating how satellite cells act in muscle regeneration is crucial for us to understand different cellular processes under the demand of tissue reorganization. The ubiquitination of transcription factors is crucial for the regulation of diverse 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 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 both positions, K48 and K63. We recently described the location of Parkin in the nucleus of muscle progenitor cells, however, it is not clear what functions Parkin may perform, as well as whether this nuclear location impacts the expression of genes related to the proliferation or differentiation of myogenic cells. Thus, the objective of the current proposal is to investigate the effects of nuclear Parkin localization in muscle 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. We intend to elucidate new Parkin interactions with target proteins of its ubiquitination, and the impact of such post-translational modifications on the expression of genes involved in the differentiation of these cells. (AU)

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