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The HIV-1 Vpr and glucocorticoid receptor complex is a gain-of-function interaction that prevents the nuclear localization of PARP-1
- Publication Year :
- 2006
-
Abstract
- The Vpr protein of HIV-1 functions as a vital accessory gene by regulating various cellular functions, including cell differentiation, apoptosis, nuclear factor of kappaB (NF-kappaB) suppression and cell-cycle arrest of the host cell. Several reports have indicated that Vpr complexes with the glucocorticoid receptor (GR), but it remains unclear whether the GR pathway is required for Vpr to function. Here, we report that Vpr uses the GR pathway as a recruitment vehicle for the NF-kappaB co-activating protein, poly(ADP-ribose) polymerase-1 (PARP-1). The GR interaction with Vpr is both necessary and sufficient to facilitate this interaction by potentiating the formation of a Vpr-GR-PARP-1 complex. The recruitment of PARP-1 by the Vpr-GR complex prevents its nuclear localization, which is necessary for Vpr to suppress NF-kappaB. The association of GR with PARP-1 is not observed with steroid (glucocorticoid) treatment, indicating that the GR association with PARP-1 is a gain of function that is solely attributed to HIV-1 Vpr. These data provide important insights into Vpr biology and its role in HIV pathogenesis.
- Subjects :
- Lipopolysaccharides
Cellular differentiation
viruses
Poly (ADP-Ribose) Polymerase-1
Gene Expression
HIV Infections
Jurkat cells
Enterotoxins
Jurkat Cells
Mice
Glucocorticoid receptor
NF-KappaB Inhibitor alpha
Chlorocebus aethiops
Protein Interaction Mapping
RNA, Small Interfering
Receptor
Mice, Inbred BALB C
NF-kappa B
virus diseases
Transfection
U937 Cells
vpr Gene Products, Human Immunodeficiency Virus
Interleukin-12
Cell biology
I-kappa B Kinase
Mifepristone
medicine.anatomical_structure
Female
I-kappa B Proteins
Poly(ADP-ribose) Polymerases
Protein Binding
Active Transport, Cell Nucleus
Biology
Article
Cell Line
Receptors, Glucocorticoid
medicine
Animals
Humans
Cell Nucleus
Antigens, Bacterial
Tumor Necrosis Factor-alpha
Gene Products, vpr
Transcription Factor RelA
Cell Biology
biochemical phenomena, metabolism, and nutrition
NFKB1
Cell nucleus
Mutation
Nuclear localization sequence
HeLa Cells
Interleukin-1
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Accession number :
- edsair.doi.dedup.....10577d7007766d7c329344d8288a8d14