HIV-1 Nef mimics an integrin receptor signal that recruits the polycomb group protein Eed to the plasma membrane.
The Nef protein of human and simian immunodeficiency virus (HIV/SIV) is believed to interfere with T cell activation signals by forming a signaling complex at the plasma membrane. Composition and function of the complex are not fully understood. Here we report that Nef recruits the Polycomb Group (PcG) protein Eed, so far known as a nuclear factor and repressor of transcription, to the membrane of cells. The Nef-induced translocation of Eed led to a potent stimulation of Tat-dependent HIV transcription, implying that Eed removal from the nucleus is required for optimal Tat function. Similar to Nef action, activation of integrin receptors recruited Eed to the plasma membrane, also leading to enhanced Tat/Nef-mediated transcription. Our results suggest a link between membrane-associated activation processes and transcriptional derepression and demonstrate how HIV exploits this mechanism.
Witte
Vanessa
V
Department of Dermatology, University of Erlangen/Nürnberg, 91052 Erlangen, Germany.
Laffert
Bernd
B
Rosorius
Olaf
O
Lischka
Peter
P
Blume
Katja
K
Galler
Gunther
G
Stilper
Andrea
A
Willbold
Dieter
D
D'Aloja
Paola
P
Sixt
Michael
M
Kolanus
Johanna
J
Ott
Melanie
M
Kolanus
Waldemar
W
Schuler
Gerold
G
Baur
Andreas S
AS
D000595:Amino Acid Sequence; D015153:Blotting, Western; D002462:Cell Membrane / Q000378:metabolism*; D002843:Chromatin / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D015693:Gene Products, nef / Q000378:metabolism* / Q000502:physiology*; D005982:Glutathione Transferase / Q000378:metabolism; D006678:HIV / Q000378:metabolism*; D006801:Humans; D016023:Integrins / Q000737:chemistry; D019169:Jurkat Cells; D008856:Microscopy, Fluorescence; D008954:Models, Biological; D008969:Molecular Sequence Data; D010957:Plasmids / Q000378:metabolism; D063151:Polycomb Repressive Complex 2; D011233:Precipitin Tests; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D021381:Protein Transport; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D012097:Repressor Proteins / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction; D013997:Time Factors; D014158:Transcription, Genetic; D020798:Two-Hybrid System Techniques; D054311:nef Gene Products, Human Immunodeficiency Virus
D002843:Chromatin; C491488:EED protein, human; D015693:Gene Products, nef; D016023:Integrins; D011993:Recombinant Fusion Proteins; D012097:Repressor Proteins; D054311:nef Gene Products, Human Immunodeficiency Virus; D063151:Polycomb Repressive Complex 2; D005982:Glutathione Transferase