Document 0475
 DOCN  M9460475
 TI    Nef induces CD4 endocytosis: requirement for a critical dileucine motif
       in the membrane-proximal CD4 cytoplasmic domain.
 DT    9404
 AU    Aiken C; Konner J; Landau NR; Lenburg ME; Trono D; Infectious Disease
       Laboratory, Salk Institute for Biological; Studies, La Jolla, California
       92037-1099.
 SO    Cell. 1994 Mar 11;76(5):853-64. Unique Identifier : AIDSLINE
       MED/94170386
 AB    CD4 is crucial for antigen-driven helper T cell signaling and is used as
       receptor by the human immunodeficiency virus (HIV). The HIV early
       protein Nef causes a loss of CD4 from cell surfaces through a previously
       undefined posttranscriptional mechanism. Here, we demonstrate that Nef
       acts by inducing CD4 endocytosis, resulting in its degradation in
       lysosomes. CD4 down-regulation is strongly enhanced by the association
       of Nef with cell membranes through myristoylation. The study of chimeric
       molecules reveals that 20 membrane-proximal residues of the CD4
       cytoplasmic domain are sufficient to confer Nef sensitivity. Within this
       region, a dileucine motif, reminiscent of an endocytosis and lysosomal
       targeting signal found in the CD3 gamma and delta chains, is crucial for
       CD4 response to Nef.
 DE    Amino Acid Sequence  Antigens, CD4/*METABOLISM  Cell Line  Comparative
       Study  Cytoplasm/METABOLISM  Down-Regulation (Physiology)  Endocytosis
       Gene Products, nef/*PHYSIOLOGY  Human  HIV-1/*METABOLISM
       Leucine/CHEMISTRY  Lysosomes/METABOLISM  Molecular Sequence Data
       Myristates/METABOLISM  Sequence Alignment  Structure-Activity
       Relationship  Support, Non-U.S. Gov't  Support, U.S. Gov't, P.H.S.
       JOURNAL ARTICLE

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).