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

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

Piguet, V
•
Wan, L
•
Borel, C
Show more
2000
Nature Cell Biology

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.

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Type
research article
DOI
10.1038/35004038
Author(s)
Piguet, V
Wan, L
Borel, C
Mangasarian, A
Demaurex, N
Thomas, G
Trono, Didier  
Date Issued

2000

Published in
Nature Cell Biology
Volume

2

Start page

163

End page

7

Subjects

Carrier Proteins

Editorial or Peer reviewed

REVIEWED

Written at

EPFL

EPFL units
LVG  
Available on Infoscience
September 5, 2005
Use this identifier to reference this record
https://infoscience.epfl.ch/handle/20.500.14299/215864
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