The extracellular release of Schistosoma mansoni HMGB1 nuclear protein is mediated by acetylation.
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.
Carneiro
Vitor Coutinho
VC
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.
de Moraes Maciel
Renata
R
de Abreu da Silva
Isabel Caetano
IC
da Costa
Rodrigo Furtado Madeira
RF
Paiva
Claudia Neto
CN
Bozza
Marcelo Torres
MT
Fantappié
Marcelo Rosado
MR
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
D024243:HMGB1 Protein; D051548:Histone Acetyltransferases