Navegando por Palavras-chave "acetylation"

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    Comparative Proteomic Analysis of Lysine Acetylation in Trypanosomes
    (Amer Chemical Soc, 2018) Moretti, Nilmar Silvio [UNIFESP]; Cestari, Igor; Anupama, Atashi; Stuart, Ken; Schenkman, Sergio [UNIFESP]
    Protein acetylation is a post-translational modification regulating diverse cellular processes. By using proteomic approaches, we identified N-terminal and epsilon-lysine acetylated proteins in Trypanosoma cruzi and Trypanosoma brucei, which are protozoan parasites that cause significant human and animal diseases. We detected 288 lysine acetylation sites in 210 proteins of procyclic form, an insect stage of T. brucei, and 380 acetylation sites in 285 proteins in the form of the parasite that replicates in mammalian bloodstream. In T. cruzi insect proliferative form we found 389 epsilon-lysine-acetylated sites in 235 proteins. Notably, we found distinct acetylation profiles according to the developmental stage and species, with only 44 common proteins between T. brucei stages and 18 in common between the two species. While K-ac proteins from T. cruzi are enriched in enzymes involved in oxidation/reduction balance, required for the parasite survival in the host, in T. brucei, most K-ac proteins are enriched in metabolic processes, essential for its adaptation in its hosts. We also identified in both parasites a quite variable N-terminal acetylation sites. Our results suggest that protein acetylation is involved in differential regulation of multiple cellular processes in Trypanosomes, contributing to our understanding of the essential mechanisms for parasite infection and survival.
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    Estudo das acetilações da histona h4 em trypanosoma cruzi
    (Universidade Federal de São Paulo (UNIFESP), 2015-05-27) Ramos, Thiago Cesar Prata [UNIFESP]; Schenkman, Sergio Schenkman [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)
    Histones have a series of post-translational modifications such as acetylation, methylation, fosforizações, ADP-ribosilações and ubiquitinações, that modulate access of these factors regulating replication processes, repair and recombination of DNA and transcription of mRNA. Histones are conserved in most eukaryotes. However, trypanosoma, which include protozoan parasites that early diverged during evolution, have very different histones, differing in sequence, charge and / or size when compared to their counterparts in eukaryotes. In addition, trypanosomatides have specific mechanisms of control of gene expression. In our laboratory we found that the acetylated histone 4 can be in three different lysines (K4, K10 and K14) and obtained antibodies that specifically recognize each of these modifications. Unpublished results from our group show that acetylation at K10 and K14 vary during the cell cycle and in states where there is DNA repair. In this project, we aim to understand the role of these changes, especially in K10 and K14 in Trypanosoma cruzi. For this we plan to: 1) analyze the effect of deacetylase inhibitors, 2) change the susceptibility of histone H4 expressing this modified protein in the parasite itself, 3) to evaluate the effect on the over-expression of acetylation and knockout of proteins involved in repair DNA, 4) identify acetylases and deacilases directly involved in these changes, and 5) generate lines that over-express or have decreased expression for these acetylases. Together, we hope to understand the relationship between acetylation of histone H4 and replication processes, DNA repair and transcription Trypanosoma.
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    Post-translational modifications of Trypanosoma cruzi histone H4
    (Elsevier B.V., 2006-12-01) Chagas da Cunha, Julia Pinheiro; Nakayasu, Ernesto Satoshi; Almeida, Igor Correia de; Schenkman, Sergio; Universidade Federal de São Paulo (UNIFESP); Univ Texas
    Histone tails provide sites for a variety of post-translational modifications implicated in the control of gene expression and chromatin assembly. As both histones and control of gene expression in trypanosomes are highly divergent compared to most eukaryotes, post-translational modifications of Trypanosoma cruzi histones were investigated. After in vivo incubation of live parasites with radiolabeled precursors, histone H4 mainly incorporates [H-3]-acetyl, and to a lesser extent [H-3]-methyl residues. in contrast, histone H3 preferentially incorporates [H-3]-methyl residues. the modifications of histone H4 were further characterized by mass spectrometry. MALDI-TOF-TOF-MS analysis revealed that peptides from histone H4 amino-terminus, obtained by either endoproteinase Glu-C or endoproteinase Arg-C digestion, contain isoforms with 14 and 42 Da additions, suggesting the presence of simultaneous acetylations and/or methylations. Tandem mass spectrometry analysis demonstrated that the N-terminal alanine is methylated, and lysine residues at positions 4, 10, 14 and 57 are acetylated; lysine at position 18 is mono-methylated, while arginine at position 53 is dimethylated. Immunoblotting analyses using specific antibodies raised against synthetic and acetylated peptides of T cruzi histone H4 indicate that lysine 4 is acetylated in the majority of histone H4, while other acetylations at the N-terminus portion of histone H4 are less abundant. (c) 2006 Elsevier B.V. All rights reserved.