

![]() |
Nef-induced CD4 degradation: a diacidic-based motif in Nef functions as a lysosomal targeting signal through the binding of beta-COP in endosomes |
|
Authors | ||
Published in | Cell. 1999, vol. 97, no. 1, p. 63-73 | |
Abstract | The Nef protein of primate lentiviruses downregulates the cell surface expression of CD4 through a two-step process. First, Nef connects the cytoplasmic tail of CD4 with adaptor protein complexes (AP), thereby inducing the formation of CD4-specific clathrin-coated pits that rapidly endocytose the viral receptor. Second, Nef targets internalized CD4 molecules for degradation. Here we show that Nef accomplishes this second task by acting as a connector between CD4 and the beta subunit of COPI coatomers in endosomes. A sequence encompassing a critical acidic dipeptide, located nearby but distinct from the AP-binding determinant of HIV-1 Nef, is responsible for beta-COP recruitment and for routing to lysosomes. A novel class of endosomal sorting motif, based on acidic residues, is thus revealed, and beta-COP is identified as its downstream partner. | |
Keywords | Amino Acid Sequence — Animals — Antigens, CD4/metabolism — Binding Sites/physiology — CHO Cells — Cell Line — Coatomer Protein — Cricetinae — Dipeptides/physiology — Down-Regulation/physiology — Endosomes/metabolism/physiology — Gene Products, nef/physiology — HIV-1/physiology — Humans — Hydrogen-Ion Concentration — Kidney — Lysosomes/metabolism/physiology — Microtubule-Associated Proteins/metabolism/physiology — Molecular Sequence Data — Signal Transduction/physiology — Nef Gene Products, Human Immunodeficiency Virus | |
Identifiers | PMID: 10199403 | |
Full text | ||
Structures | ||
Research groups | Obésité et syndrome métabolique (803) Signaux intracellulaires (210) | |
Citation (ISO format) | PIGUET, Vincent et al. Nef-induced CD4 degradation: a diacidic-based motif in Nef functions as a lysosomal targeting signal through the binding of beta-COP in endosomes. In: Cell, 1999, vol. 97, n° 1, p. 63-73. https://archive-ouverte.unige.ch/unige:30336 |