Gene modulation of RIPK3 and MLKL and its impact in the sensibility to death by necroptosis

• Grant number: 17/25009-1
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• Start date: March 01, 2018
• End date: November 15, 2020
• Field of knowledge: Biological Sciences - Immunology - Cellular Immunology
• Principal Investigator: Ricardo Weinlich
• Grantee: Larissa Cardoso Zanetti
• Host Institution: Instituto Israelita de Ensino e Pesquisa Albert Einstein (IIEPAE). Sociedade Beneficente Israelita Brasileira Albert Einstein (SBIBAE). São Paulo , SP, Brazil
• Associated scholarship(s): 19/13813-6 - High throughput mapping of MLKL transcriptional regulatory elements, BE.EP.DD

Abstract

Necroptosis is a recently discovered, biochemically-controlled, cell death pathway that is independent of caspases and present morphological hallmarks similar to those of accidental necrosis. It can be activated by different stimuli, including death receptors and TRIF-mediated signals, and involves sequential phosphorylation of RIPK1 and RIPK3 kinases as well the MLKL pseudokinase. The role of necroptosis was already demonstrated in many pathophysiological conditions, including bacterial and viral infections, cancer, ischemic insults and autoimmune disease. In many of these settings, the levels of RIPK3 and MLKL expression was shown to vary significantly, either positively or negatively. Also, these levels correlated to the sensitivity towards necroptotic stimuli. Surprisingly, however, data concerning the signaling pathways and transcription factors involved in neither this regulation nor the characterization of RIPK3 and MLKL promoter regions is very scarce. Therefore, this project has the objective of shedding light on the mechanisms of RIPK3 and MLKL transcriptional modulation through promoter region studies as well the characterization of the transcription factors involved in their regulation. (AU)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

VELIMIROVIC, MINJA; ZANETTI, LARISSA C.; SHEN, MAX W.; FIFE, JAMES D.; LIN, LIN; CHA, MINSUN; AKINCI, ERSIN; BARNUM, DANIELLE; YU, TIAN; SHERWOOD, RICHARD I.. Peptide fusion improves prime editing efficiency. NATURE COMMUNICATIONS, v. 13, n. 1, p. 8-pg., 2022-06-18. (17/25009-1, 19/13813-6)

ZANETTI, LARISSA C.; WEINLICH, RICARDO; FLOREZ, AF; ALBORZINIA, H. Necroptosis, the Other Main Caspase-Independent Cell Death. FERROPTOSIS: MECHANISM AND DISEASES, v. 1301, p. 16-pg., 2021-01-01. (17/25009-1, 16/17628-0)