title: The extracellular release of Schistosoma mansoni HMGB1 nuclear protein is mediated by acetylation.
abstract: Schistosoma mansoni HMGB1 (SmHMGB1) was revealed to be a substrate for the parasite histone acetyltransferases SmGCN5 and SmCBP1. We found that full-length SmHMGB1, as well as its HMG-box B (but not HMG-box A) were acetylated in vitro by SmGCN5 and SmCBP1. However, SmCBP1 was able to acetylate both substrates more efficiently than SmGCN5. Interestingly, the removal of the C-terminal acidic tail of SmHMGB1 (SmHMGB1DeltaC) resulted in increased acetylation of the protein. We showed by mammalian cell transfection assays that SmHMGB1 and SmHMGB1DeltaC were transported from the nucleus to the cytoplasm after sodium butyrate (NaB) treatment. Importantly, after NaB treatment, SmHMGB1 was also present outside the cell. Together, our data suggest that acetylation of SmHMGB1 plays a role in cellular trafficking, culminating with its secretion to the extracellular milieu. The possible role of SmHMGB1 acetylation in the pathogenesis of schistosomiasis is discussed.
authors.affiliation: Instituto de Bioquímica Médica, Programa de Biotecnologia e Biologia Molecular, Universidade Federal do Rio de Janeiro, CCS, Ilha do Fundão, Rio de Janeiro 21941-590, Brazil.
authors.forename: Vitor Coutinho
authors.initials: VC
authors.lastname: Carneiro
authors.forename: Renata
authors.initials: R
authors.lastname: de Moraes Maciel
authors.forename: Isabel Caetano
authors.initials: IC
authors.lastname: de Abreu da Silva
authors.forename: Rodrigo Furtado Madeira
authors.initials: RF
authors.lastname: da Costa
authors.forename: Claudia Neto
authors.initials: CN
authors.lastname: Paiva
authors.forename: Marcelo Torres
authors.initials: MT
authors.lastname: Bozza
authors.forename: Marcelo Rosado
authors.initials: MR
authors.lastname: Fantappié
mesh_terms: D000107:Acetylation; D021581:Active Transport, Cell Nucleus; D000818:Animals; D002467:Cell Nucleus / Q000378:metabolism*; D002478:Cells, Cultured; D024243:HMGB1 Protein / Q000378:metabolism*; D051548:Histone Acetyltransferases / Q000378:metabolism*; D012550:Schistosoma mansoni / Q000378:metabolism*; D012555:Schistosomiasis mansoni / Q000469:parasitology
chemical_list: D024243:HMGB1 Protein; D051548:Histone Acetyltransferases