Nef induces apoptosis by activating JNK signaling pathway and inhibits NF-kB-dependent immune responses in Drosophila

Cited 22 time in webofscience Cited 0 time in scopus
  • Hit : 596
  • Download : 489
The human immunodeficiency virus type 1 (HIV-1) nef gene encodes a 27-kDa protein that plays a crucial role during AIDS pathogenesis, but its exact functional mechanism has not been fully elucidated and remains controversial. The present study illuminated the in vivo functions of Nef using Drosophila, in which genetic analyses can be conveniently conducted. Using Drosophila transgenic lines for wild-type Nef, we demonstrated that Nef is not involved in the regulation of cell proliferation but rather specifically induces caspase-dependent apoptosis in wings in a cell-autonomous manner. Interestingly, myristoylation-defective Nef completely failed to induce the apoptotic wing phenotypes, consistent with previous reports demonstrating a crucial role for membrane localization of Nef in vivo. Further genetic and immunohistochemical studies revealed that Nef-dependent JNK activation is responsible for apoptosis. Furthermore, we found that ectopic expression of Nef inhibits Drosophila innate immune responses including Relish NF-kB activation with subsequent induction of an antimicrobial peptide, diptericin. The in vivo functions of Nef in Drosophila are highly consistent with those found in mammals and so we propose that Nef regulates evolutionarily highly conserved signaling molecules of the JNK and NF-kB signaling pathways at the plasma membrane, and consequently modulates apoptosis and immune responses in HIV target cells.
Publisher
Company Of Biologists Ltd
Issue Date
2005-05
Language
English
Article Type
Article
Keywords

KAPPA-B; HIV-1 NEF; T-CELLS; C-JUN; TERMINAL KINASE; PROTEIN; EXPRESSION; INDUCTION; INFECTION; DEATH

Citation

JOURNAL OF CELL SCIENCE, v.118, no.9, pp.1851 - 1859

ISSN
0021-9533
DOI
10.1242/jcs.02312
URI
http://hdl.handle.net/10203/6174
Appears in Collection
BS-Journal Papers(저널논문)
Files in This Item
000229458700010.pdf(490.93 kB)Download
This item is cited by other documents in WoS
⊙ Detail Information in WoSⓡ Click to see webofscience_button
⊙ Cited 22 items in WoS Click to see citing articles in records_button

qr_code

  • mendeley

    citeulike


rss_1.0 rss_2.0 atom_1.0