Adriano Monte-Alegre, Vergnes Baptiste, Poncet Joel, Mathieu-Daude Françoise, da Silva Anabela Cordeiro, Ouaissi Ali, Sereno Denis
UR008 Pathogénie des Trypanosomatidés, Centre IRD de Montpellier, 911 Avenue Agropolis, Montpellier, 34394, France.
Parasitol Res. 2007 Mar;100(4):811-8. doi: 10.1007/s00436-006-0352-3. Epub 2006 Nov 10.
The cytoplasmic Leishmania silent information regulator 2 (SIR2)RP1 protein is essential for parasite growth and survival and constitutes an attractive therapeutic target. Little information is available on putative substrate(s) and/or partner(s) that could shed light on the pathways in which this enzyme plays a role. We carried out co-immunoprecipitation experiments on the soluble fractions of wild-type and parasites overexpressing LmSIR2RP1 and found that the essential chaperone heat shock protein (HSP) 83, the Leishmania ortholog of the mammalian HSP90, constantly co-immunoprecipitated with LmSIR2RP1. We found that Leishmania HSP83 is among the lysine acetylated protein, but the intracellular level of SIR2RP1 does not influence the acetylation status of HSP83. Finally, the modified Geldanamycin susceptibility (an inhibitor of HSP83) exhibited by SIR2RP1 mutant parasites support an in vivo relationship between the chaperone activity of HSP83 and LmSIR2RP1. An insight on the nature of the interaction in Leishmania is required to understand its role in the cell fate control during cytodifferentiation.
细胞质利什曼原虫沉默信息调节因子2（SIR2）RP1蛋白对寄生虫的生长和存活至关重要，是一个有吸引力的治疗靶点。关于可能揭示该酶所参与途径的假定底物和/或伙伴，目前所知甚少。我们对野生型和过表达LmSIR2RP1的寄生虫的可溶性部分进行了免疫共沉淀实验，发现必需的伴侣热休克蛋白（HSP）83（哺乳动物HSP90的利什曼原虫直系同源物）始终与LmSIR2RP1共免疫沉淀。我们发现利什曼原虫HSP83是赖氨酸乙酰化蛋白之一，但SIR2RP1的细胞内水平并不影响HSP83的乙酰化状态。最后，SIR2RP1突变寄生虫表现出的改良格尔德霉素敏感性（一种HSP83抑制剂）支持了HSP83的伴侣活性与LmSIR2RP1之间的体内关系。为了理解其在细胞分化过程中对细胞命运控制的作用，需要深入了解利什曼原虫中相互作用的本质。
