A novel human WD protein, h-beta TrCp, that interacts with HIV-1 Vpu connects CD4 to the ER degradation pathway through an F-box motif.
HIV-1 Vpu interacts with CD4 in the endoplasmic reticulum and triggers CD4 degradation, presumably by proteasomes. Human beta TrCP identified by interaction with Vpu connects CD4 to this proteolytic machinery, and CD4-Vpu-beta TrCP ternary complexes have been detected by coimmunoprecipitation. beta TrCP binding to Vpu and its recruitment to membranes require two phosphoserine residues in Vpu essential for CD4 degradation. In beta TrCP, WD repeats at the C terminus mediate binding to Vpu, and an F box near the N terminus is involved in interaction with Skp1p, a targeting factor for ubiquitin-mediated proteolysis. An F-box deletion mutant of beta TrCP had a dominant-negative effect on Vpu-mediated CD4 degradation. These data suggest that beta TrCP and Skp1p represent components of a novel ER-associated protein degradation pathway that mediates CD4 proteolysis.
Margottin
F
F
CJF 97-03 INSERM, Institut Cochin de Génétique Moléculaire, Université Paris V, Faculté de médecine Cochin, France.
Bour
S P
SP
Durand
H
H
Selig
L
L
Benichou
S
S
Richard
V
V
Thomas
D
D
Strebel
K
K
Benarous
R
R
D001665:Binding Sites / Q000276:immunology; D015704:CD4 Antigens / Q000378:metabolism*; D018797:Cell Cycle Proteins / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000737:chemistry / Q000378:metabolism* / Q000821:virology; D019204:GTP-Binding Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D015497:HIV-1; D054298:Human Immunodeficiency Virus Proteins; D006801:Humans; D019169:Jurkat Cells; D008969:Molecular Sequence Data; D016296:Mutagenesis / Q000502:physiology; D012091:Repetitive Sequences, Nucleic Acid; D044786:S-Phase Kinase-Associated Proteins; D017386:Sequence Homology, Amino Acid; D012694:Serine / Q000378:metabolism; D014452:Ubiquitins / Q000378:metabolism; D054334:Viral Regulatory and Accessory Proteins / Q000378:metabolism*; D044844:beta-Transducin Repeat-Containing Proteins; D000086082:Viroporin Proteins
D015704:CD4 Antigens; D018797:Cell Cycle Proteins; D019204:GTP-Binding Proteins; D054298:Human Immunodeficiency Virus Proteins; D044786:S-Phase Kinase-Associated Proteins; D012694:Serine; D014452:Ubiquitins; D054334:Viral Regulatory and Accessory Proteins; D044844:beta-Transducin Repeat-Containing Proteins; C471644:BTRC protein, human; C514859:vpu protein, Human immunodeficiency virus 1; D000086082:Viroporin Proteins