Investigation of the effects of RhoA and RhoC silencing in p53 protein subcellular localization of leukemia cells treated with UV-C light

• Grant number: 22/16158-1
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: March 01, 2023
• End date: February 28, 2025
• Field of knowledge: Health Sciences - Medicine
• Principal Investigator: Mariana Lazarini
• Grantee: Amanda Damasceno Ferreira
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil

Abstract

Acute Myeloid Leukemia (AML) is a cancer originated from the accumulation of immature hematopoietic cells (blasts) in the bone marrow, characterized by low rates of patient survival. Mutations in the tumor suppressing gene TP53 are present in around 5-10% of AML cases and are associated with a worse prognosis. It is believed that the additional patients present inactivation of the TP53 pathway by other mechanisms. The nucleocytoplasmic localization of p53 is essential for its activity as a transcription factor, but its regulation is not completely understood. Evidence points that the Rho GTPases proteins RhoA and RhoC are involved in the regulation p53 activity. RhoA and RhoC are known for controlling the cytoskeleton rearrangement, participating in cellular functions essentially controlled by p53. However, the relation between these proteins and the p53 subcellular localization was not yet investigated in leukemia cells.This project's goal is to investigate the effects of RhoA and RhoC silencing in the subcellular localization of p53 in leukemia cells. Cell lineages will be silenced for RhoA and RhoC with lentivirus and the subcellular location of p53 will be investigated through confocal microscopy. P53 expression will be induced by UV-C treatment. The results of this project will contribute for the elucidation of the functions of RhoA and RhoC in the signaling pathway of p53. Along with other data from our group, this study will contribute for a greater understanding of the role of Rho GTPases and p53 in AML.