HIV Tat binds Egr proteins and enhances Egr-dependent transactivation of the Fas ligand promoter.
HIV Tat can enhance activation-induced up-regulation of Fas ligand (FasL), which may contribute to T cell apoptosis in human immune deficiency virus (HIV)-infected individuals. We have assessed functional and physical interactions between Tat and the Egr family of transcription factors (Egr-1, -2, and -3), the latter two of which are major participants in activation-induced FasL up-regulation. Here we report that whereas Tat itself has no effect on the FasL promoter, it binds to Egr-2 and -3 and synergizes with them to superinduce expression of a FasL promoter-driven reporter. A Tat molecule containing a single amino acid substitution that results in the loss of transactivation activity for the HIV long terminal repeat still binds Egr-3 but can no longer enhance Egr-mediated transactivation of the FasL promoter. Furthermore, the mutated Tat acts as a dominant negative inhibitor, blocking the superinduction of FasL caused by wild type Tat. Because Tat is present in virus-infected cells and in the serum of HIV-infected individuals, these results suggest that increased expression of FasL in these circumstances may result from the cooperative activities of activation-induced Egrs and Tat.
Yang
Yili
Y
Laboratory of Immune Cell Biology, NCI, National Institutes of Health, Bethesda, Maryland 20892, USA.
Dong
Bei
B
Mittelstadt
Paul R
PR
Xiao
Hua
H
Ashwell
Jonathan D
JD
D018076:DNA, Complementary / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism*; D051767:Early Growth Response Protein 2; D051776:Early Growth Response Protein 3; D053222:Fas Ligand Protein; D015696:Gene Products, tat / Q000378:metabolism*; D005982:Glutathione Transferase / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D015151:Immunoblotting; D008156:Luciferases / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000378:metabolism*; D009154:Mutation; D010957:Plasmids / Q000378:metabolism; D011233:Precipitin Tests; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D014176:Protein Biosynthesis; D014157:Transcription Factors / Q000378:metabolism*; D015533:Transcriptional Activation
D018076:DNA, Complementary; D004268:DNA-Binding Proteins; C497326:EGR2 protein, human; D051767:Early Growth Response Protein 2; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D015696:Gene Products, tat; D008562:Membrane Glycoproteins; D014157:Transcription Factors; D051776:Early Growth Response Protein 3; D008156:Luciferases; D005982:Glutathione Transferase