AEGiS-05CROI: A novel human protein that interacts with HIV-1 Vpu, connects CD4 to the ER degradation pathway.

5th Conference on Retroviruses and Opportunistic Infections


Chicago, IL - February 1-5, 1998



A novel human protein that interacts with HIV-1 Vpu, connects CD4 to the ER degradation pathway.

Conf Retroviruses Opportunistic Infect 1998 Feb 1-5; 5th:83 (abstract no. 25)

Margottin F, Bour SP, Durand H, Strebel K, Benarous R; INSERM, ICGM, Paris, France.

We used the yeast two-hybrid system to identify cellular proteins that interact with HIV-1 Vpu and could act as mediators of Vpu function. HIV-1 Vpu interacts with CD4 in the endoplasmic reticulum and triggers CD4 degradation by a mechanism that presumably involves proteasomes. A novel human protein was characterized by specific interaction with Vpu, including two-hybrid assay, in vitro binding and co-immunoprecipitation in cells expressing transiently Vpu. We had evidence that this interaction is probably responsible for the targeting of CD4 to the proteolytic machinery. This protein can be recruited to microsomal membranes by Vpu. Its interaction with Vpu and its recruitment to membranes require the presence of two Vpu phospho-serine residues S52 and S56 essential for CD4 degradation. Domains of this protein respectively responsible for binding to Vpu and for targeting to proteolysis could be mapped. These data suggest that such Vpu-binding protein could play the role of cellular mediator of Vpu activity on CD4 degradation.

Keywords: AEGIS, Antigens, CD4, Gene Products, vpu, HIV-1, Endoplasmic Reticulum, Receptors, Estrogen, Cysteine Endopeptidases, Multienzyme Complexes, Protein Binding, Phosphorylation, Biological Transport, multicatalytic endopeptidase complex, Human, In Vitro, Animal, metabolism, AIDS

1998-02-01
25

Copyright © 1998 - Foundation for Retrovirology and Human Health (IAS). Reproduction of this abstract (other than one copy for personal reference) must be cleared through the Foundation for Retrovirology and Human Health. Licensed from National Library of Medicine.