title: A novel acyl-CoA thioesterase enhances its enzymatic activity by direct binding with HIV Nef.
abstract: 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.
authors.affiliation: Division of Molecular Genetics, Chiba University School of Medicine, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Watanabe
authors.forename: T
authors.initials: T
authors.lastname: Shiratori
authors.forename: H
authors.initials: H
authors.lastname: Shoji
authors.forename: S
authors.initials: S
authors.lastname: Miyatake
authors.forename: Y
authors.initials: Y
authors.lastname: Okazaki
authors.forename: K
authors.initials: K
authors.lastname: Ikuta
authors.forename: T
authors.initials: T
authors.lastname: Sato
authors.forename: T
authors.initials: T
authors.lastname: Saito
mesh_terms: D000595:Amino Acid Sequence; D001665:Binding Sites; D003001:Cloning, Molecular; D004347:Drug Interactions; D015693:Gene Products, nef / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D006678:HIV / Q000201:enzymology* / Q000502:physiology; D006801:Humans; D019169:Jurkat Cells; D008969:Molecular Sequence Data; D010170:Palmitoyl-CoA Hydrolase / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D011485:Protein Binding; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D013379:Substrate Specificity; D054311:nef Gene Products, Human Immunodeficiency Virus
chemical_list: D015693:Gene Products, nef; D011994:Recombinant Proteins; D054311:nef Gene Products, Human Immunodeficiency Virus; D010170:Palmitoyl-CoA Hydrolase