title: Upregulation of the apoptosis-associated protein Grb3-3 in HIV-1-infected human CD4(+) lymphocytes.
abstract: The mechanism(s) by which HIV-1 infection contributes to depletion of CD4(+) T cell is not well understood. In this report, we investigated whether a recently identified isoform of growth factor receptor bound protein (Grb2), named Grb3-3, a signaling molecule that is associated with the MAP kinase pathway and with apoptosis could be involved. We find that Grb3-3 is markedly up-regulated following HIV-1 infection of CD4(+) peripheral blood mononuclear cells undergoing apoptosis. Although IL-2 deprived CD4(+) cells also undergo apoptosis to a similar extent, Grb3-3 upregulation is not detected under these experimental conditions. Transient overexpression of Grb3-3 in Jurkat T-cells also causes apoptosis. Upon staurosporine stimulation, Grb3-3 predisposes Sup-T1 cell to apoptosis. Finally, analysis of the HIV-1 genes responsible for Grb3-3 expression demonstrates that Tat and Nef can independently induces its expression, suggesting these two earliest viral gene products of HIV-1 may share some common pathway(s) in up-regulating Grb3-3 expression.
authors.affiliation: Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Boston, Massachusetts 02115, USA.
authors.forename: X
authors.initials: X
authors.lastname: Li
authors.forename: M C
authors.initials: MC
authors.lastname: Multon
authors.forename: Y
authors.initials: Y
authors.lastname: Henin
authors.forename: F
authors.initials: F
authors.lastname: Schweighoffer
authors.forename: C
authors.initials: C
authors.lastname: Venot
authors.forename: J
authors.initials: J
authors.lastname: LaVecchio
authors.forename: J
authors.initials: J
authors.lastname: Josef
authors.forename: P
authors.initials: P
authors.lastname: Stuckert
authors.forename: A
authors.initials: A
authors.lastname: Mhashilkar
authors.forename: B
authors.initials: B
authors.lastname: Tocqué
authors.forename: W A
authors.initials: WA
authors.lastname: Marasco
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D017209:Apoptosis / Q000235:genetics; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D051380:GRB2 Adaptor Protein; D015658:HIV Infections / Q000235:genetics / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D015497:HIV-1; D006801:Humans; D014176:Protein Biosynthesis; D011506:Proteins / Q000235:genetics; D015854:Up-Regulation
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D051380:GRB2 Adaptor Protein; C495948:GRB2 protein, human; D011506:Proteins