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HIV-1 Nef protein binds to the cellular protein PACS-1 to downregulate class I major histocompatibility complexes

Wan, L
Thomas, G
Published in Nature cell biology. 2000, vol. 2, no. 3, p. 163-7
Abstract Major-histocompatibility-complex (MHC) proteins are used to display, on the surface of a cell, peptides derived from foreign material - such as a virus - that is infecting that cell. Cytotoxic T lymphocytes then recognize and kill the infected cell. The HIV-1 Nef protein downregulates the cell-surface expression of class I MHC proteins, and probably thereby promotes immune evasion by HIV-1. In the presence of Nef, class I MHC molecules are relocalized from the cell surface to the trans-Golgi network (TGN) through as-yet-unknown mechanisms. Here we show that Nef-induced downregulation of MHC-I expression and MHC-I targeting to the TGN require the binding of Nef to PACS-1, a molecule that controls the TGN localization of the cellular protein furin. This interaction is dependent on Nef's cluster of acidic amino acids. A chimaeric integral membrane protein containing Nef as its cytoplasmic domain localizes to the TGN after internalization, in an acidic-cluster- and PACS-1-dependent manner. These results support a model in which Nef relocalizes MHC-I by acting as a connector between MHC-I's cytoplasmic tail and the PACS-1-dependent protein-sorting pathway.
Keywords AnimalsAntigens, CD4/metabolismCapsid/antagonists & inhibitors/metabolismCarrier ProteinsCell LineDown-Regulation/drug effects/physiologyEndocytosis/drug effects/geneticsFurinGene Expression Regulation/drug effects/geneticsGene Products, nef/metabolism/pharmacologyGolgi Apparatus/metabolismHIV-1/metabolismHistocompatibility Antigens Class I/metabolismHumansHydrogen-Ion ConcentrationMelanoma/metabolism/pathologyMembrane Proteins/metabolismOligonucleotides, Antisense/pharmacologyProtein Structure, Tertiary/geneticsRatsReceptor, IGF Type 2/metabolismRecombinant Fusion Proteins/genetics/metabolismSubtilisins/metabolismTransfectionVesicular Transport ProteinsNef Gene Products, Human Immunodeficiency Virus
PMID: 10707087
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Research group Signaux intracellulaires (210)
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PIGUET, Vincent et al. HIV-1 Nef protein binds to the cellular protein PACS-1 to downregulate class I major histocompatibility complexes. In: Nature cell biology, 2000, vol. 2, n° 3, p. 163-7. doi: 10.1038/35004038 https://archive-ouverte.unige.ch/unige:30339

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Deposited on : 2013-10-11

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