Degron Pathways and Leishmaniasis: Debating Potential Roles of Leishmania spp. Proteases Activity on Guiding Hosts Immune Response and Their Relevance to the Development of Vaccines

• Published in: Vaccines (Basel) Vol. 11; no. 6; p. 1015
• Main Authors: Oliveira, Adriane Silva, Aredes-Riguetti, Lara Mata, Pereira, Bernardo Acácio Santini, Alves, Carlos Roberto, Souza-Silva, Franklin
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 23.05.2023; MDPI
• Subjects: Activator protein 1; Biodegradation; Cyclic AMP response element-binding protein; cysteine proteases; Cytokines; Degradation; degron; Enzymes; Immune response; Immune system; Immunoregulation; Interleukin 13; Interleukin 17; Interleukin 4; Interleukin 5; Leishmania; Leishmania spp; Leishmaniasis; Lymphocytes T; NF-κB protein; Parasites; Parasitic diseases; Physiology; Proteins; Protozoa; serine proteases; Serine proteinase; Stat1 protein; Substrates; Three dimensional models; Transcription factors; Vaccines; Vector-borne diseases; Virulence; immune response; transcription factors; cytokines; cysteine proteases; serine proteases; Leishmania spp; degron
• ISSN: 2076-393X; 2076-393X
• DOI: 10.3390/vaccines11061015

Degrons are short peptide sequences that signalize target sites for protein degradation by proteases. Herein, we bring forth the discussion on degrons present in proteins related to the immune system of that are potential targets for cysteine and serine proteases of spp. and their possible roles on host immune regulation by parasites. The Merops database was used to identify protease substrates and proteases sequence motifs, while MAST/MEME Suite was applied to find degron motifs in murine cytokines (IFN-y, IL-4, IL-5, IL-13, IL-17) and transcription factors (NF-kappaB, STAT-1, AP-1, CREB, and BACH2). STRING tool was used to construct an interaction network for the immune factors and SWISS-MODEL server to generate three-dimensional models of proteins. In silico assays confirm the occurrence of degrons in the selected immune response factors. Further analyses were conducted only in those with resolved three-dimensional structures. The predicted interaction network of degron-containing proteins shows the possibility that the specific activity of parasite proteases could interfere with the trend of Th1/Th2 immune responses. Data suggest that degrons may play a role in the immune responses in leishmaniases as targets for parasite proteases activity, directing the degradation of specific immune-related factors.