@article{PAR00003116, title = {{T}he {L}eishmania infantum cytosolic {SIR}2-related protein 1 ({L}i{SIR}2{RP}1) is an {NAD}(+)-dependent deacetylase and {ADP}-ribosyltransferase}, author = {{T}avares, {J}oana and {O}uaissi, {A}li and {S}antarem, {N}. and {S}ereno, {D}enis and {V}ergnes, {B}aptiste and {S}ampaio, {P}. and {C}ordeiro-{D}a-{S}ilva, {A}.}, editor = {}, language = {{ENG}}, abstract = {{P}roteins of the {SIR}2 ({S}ilent {I}nformation {R}egulator 2) family are characterized by a conserved catalytic domain that exerts unique {NAD}+-dependent deacetylase activity on histones and various other cellular substrates. {P}revious reports from us have identified a {L}eishmania infantum gene encoding a cytosolic protein termed {L}i{SIR}2{RP}1 ({L}eishmania infantum {SIR}2-related protein 1) that belongs to the {SIR}2 family. {T}argeted disruption of one {L}i{SIR}2{RP}1 gene allele led to decreased amastigote virulence, in vitro as well as in vivo. {I}n the present study, attempts were made for the first time to explore and characterize the enzymatic functions of {L}i{SIR}2{RP}1. {T}he {L}i{SIR}2{RP}1 exhibited robust {NAD}(+)-dependent deacetylase and {ADP}-ribosyltransferase activities. {M}oreover, {L}i{SIR}2{RP}1 is capable of deacetylating tubulin, either in dimers or, when present, in taxol-stabilized microtubules or in promastigote and amastigote extracts. {F}urthermore, the immunostaining of parasites revealed a partial co-localization {O}f alpha-tubulin and {L}i{SIR}2{RP}1 with punctate labelling, seen on the periphery of both promastigote and amastigote stages. {I}solated parasite cyto skeleton reacted with antibodies showed that part of {L}i{SIR}2{RP}1 is associated to the cytoskeleton network of both promastigote and amastigote forms. {M}oreover, the {W}estern blot analysis of the soluble and insoluble fractions of the detergent of prornastigote and amastigote forms revealed the presence of alpha-tubulin in the insoluble fraction, and the {L}i{SIR}2{RP}1 distributed in both soluble and insoluble fractions of promastigotes its well as amastigotes. {C}ollectively, the results of the present study demonstrate that {L}i{SIR}2{RP}1 is an {NAD}(+)-dependent deacetylase that also exerts an {ADP}-ribosyltransferase activity. {T}he fact that tall could be among the targets of {L}i{SIR}2{RP}1 may have significant implications during the remodelling of the morphology of the parasite and its interaction with the host cell.}, keywords = {{A}dp-ribosyltransferase ; {C}ytoskeleton ; {L}eishmania infantum sir2-related protein 1 (lisir2rp1) ; {N}ad(+)-dependent deacetylase ; {P}arasite ; {A}lpha-tubulin}, booktitle = {}, journal = {{B}iochemical {J}ournal}, volume = {415}, numero = {{P}art 3}, pages = {377--386}, ISSN = {0264-6021}, year = {2008}, DOI = {10.1042/bj20080666}, URL = {https://www.documentation.ird.fr/hor/{PAR}00003116}, }