Mechanisms of formation of Bclaf1 biomolecular condensates in cardiac myocytes under oxidative stress

• Grant number: 24/21858-8
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• Start date: June 01, 2025
• End date: July 31, 2028
• Field of knowledge: Biological Sciences - Morphology - Cytology and Cell Biology
• Principal Investigator: Aline Mara dos Santos
• Grantee: Beatriz Rocha Ilídio Rodrigues
• Host Institution: Instituto de Biologia (IB). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil

Abstract

Cardiovascular complications arising from antineoplastic therapies have become an emerging public health issue due to the growing population of cancer survivors. Cardiotoxicity induced by chemotherapeutic agents commonly used to treat various neoplasms, such as doxorubicin (dox), is a severe condition that can progress to chronic cardiomyopathy, congestive heart failure, and patient death. Protein Quality Control (PQC) is essential for maintaining cellular homeostasis, ensuring proper protein conformation and function, and regulating the synthesis, folding, and degradation of damaged or misfolded proteins.Bcl-2-associated transcription factor 1 (Bclaf1/Btf) is a protein belonging to the family that regulates cell death. However, various studies have highlighted its role in other processes independent of apoptosis. Previous findings have shown that Bclaf1 interacts with focal adhesion kinase 2 (PTK2/FAK) in the nucleus, forming biomolecular condensates where Bclaf1 protects PTK2 from degradation during oxidative stress caused by doxorubicin (dox), an event crucial for cardiomyocyte survival.However, the mechanism by which Bclaf1 biomolecular condensates are regulated remains unclear. In this study, we propose to investigate the role of intranuclear PQC pathways to uncover the Bclaf1-dependent survival mechanisms and those involved in the pathogenesis of dox-induced cardiotoxicity, with potential applicability in the medical field. (AU)