The Leishmania infantum cytosolic SIR2 related protein 1 (LiSIR2RP1) is an NAD+-dependent deacetylase and ADP-ribosyltransferase - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue Biochemical Journal Année : 2008

The Leishmania infantum cytosolic SIR2 related protein 1 (LiSIR2RP1) is an NAD+-dependent deacetylase and ADP-ribosyltransferase

Joana Tavares
  • Fonction : Auteur
Ali Ouaissi
  • Fonction : Auteur
Nuno Santarém
  • Fonction : Auteur
Denis Sereno
  • Fonction : Auteur
Baptiste Vergnes
Paula Sampaio
  • Fonction : Auteur

Résumé

Proteins of the SIR2 family are characterized by a conserved catalytic domain that exerts unique NAD+-dependent deacetylase activity on histone and various other cellular substrates. Previous reports from our team have identified a Leishmania infantum gene encoding a cytosolic protein termed LiSIR2RP1 that belongs to the SIR2 family. Targeted disruption of one LiSIR2RP1 gene allele led to decreased amastigote virulence, in vitro as well as in vivo. In the present study, attempts were made for the first time to explore and characterize the LiSIR2RP1 enzymatic functions. The LiSIR2RP1 exhibited robust NAD+-dependent deacetylase and ADP-ribosyltransferase activities. Moreover, LiSIR2RP1 is capable of deacetylating tubulin, either in dimers or, when present, in taxol-stabilized microtubules or in promastigote and amastigote extracts. Furthermore, the immunostaining of parasites revealed a partial co-localization of α-tubulin and LiSIR2RP1 with punctuate labelling, seen on the periphery of both promastigote and amastigote stages. Isolated parasite cytoskeleton reacted with antibodies showed that part of LiSIR2RP1 is associated to the cytoskeleton network of both promastigote and amastigote forms. Moreover, the Western blot analysis of the detergent's soluble and insoluble fractions of promastigote and amastigote forms revealed the presence of α-tubulin in the insoluble fraction, and the LiSIR2RP1 distributed in both soluble and insoluble fractions of promastigotes as well as amastigotes. Collectively, our results demonstrate that LiSIR2RP1 is an NAD+-dependent deacetylase that also exerts an ADP-ribosyltransferase activity. The fact that tubulin could be among the targets of LiSIR2RP1 may have significant implications during the remodelling of the parasite's morphology and its interaction with the host cell.

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Dates et versions

hal-00479004 , version 1 (30-04-2010)

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Joana Tavares, Ali Ouaissi, Nuno Santarém, Denis Sereno, Baptiste Vergnes, et al.. The Leishmania infantum cytosolic SIR2 related protein 1 (LiSIR2RP1) is an NAD+-dependent deacetylase and ADP-ribosyltransferase. Biochemical Journal, 2008, 415 (3), pp.377-386. ⟨10.1042/BJ20080666⟩. ⟨hal-00479004⟩

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