Watanabe H, Shiratori T, Shoji H, Miyatake S, Okazaki Y, Ikuta K, Sato T, Saito T
Division of Molecular Genetics, Chiba University School of Medicine, Japan.
Biochem Biophys Res Commun. 1997 Sep 8;238(1):234-9. doi: 10.1006/bbrc.1997.7217.
In addition to playing a crucial role in the pathogenesis of AIDS, HIV nef induces down-regulation of CD4 expression and TCR signaling and also regulates the sorting pathway in host T cells. To elucidate the Nef function in HIV progression, we searched for a cellular component which interacts with Nef. A human cDNA encoding a novel acyl-CoA thioesterase (hACTE-III) was isolated as an HIV nef-binding protein by yeast two-hybrid system. hACTE-III is homologous to E. coli thioesterase II but to none of the mammalian thioesterases and therefore belongs to a new type. hACTE-III exhibits enzymatic specificity for a broad range of fatty acyl-CoAs. The hACTE-III-binding region within Nef is localized in the central region (amino acids 109-152). hACTE-III greatly enhances its enzymatic activity upon direct binding to Nef. Considering that either Nef-overexpression or impaired fatty acid regulation induces alteration of subcellular morphology, the augmented hACTE-III function by Nef-binding might induce dysfunction of T cells.
除了在艾滋病发病机制中起关键作用外，HIV Nef还可诱导CD4表达下调和TCR信号传导，并调节宿主T细胞中的分选途径。为了阐明Nef在HIV进展中的功能，我们寻找了一种与Nef相互作用的细胞成分。通过酵母双杂交系统分离出一种编码新型酰基辅酶A硫酯酶（hACTE-III）的人cDNA作为HIV Nef结合蛋白。hACTE-III与大肠杆菌硫酯酶II同源，但与任何哺乳动物硫酯酶都不同源，因此属于一种新型。hACTE-III对多种脂肪酰基辅酶A表现出酶特异性。Nef内的hACTE-III结合区域位于中央区域（氨基酸109-152）。hACTE-III与Nef直接结合后可大大增强其酶活性。考虑到Nef过表达或脂肪酸调节受损都会诱导亚细胞形态改变，Nef结合增强的hACTE-III功能可能会诱导T细胞功能障碍。
