What question did this study set out to answer?

To determine the molecular mechanism by which the HIV-1 accessory protein Vpr activates transcription from viral and glucocorticoid-responsive promoters.

September 3, 2002Journal of VirologyOpen Access

Human Immunodeficiency Virus Type 1 (HIV-1) Accessory Protein Vpr Induces Transcription of the HIV-1 and Glucocorticoid-Responsive Promoters by Binding Directly to p300/CBP Coactivators

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Authors

TKTomoshige KinoQatar Airways (Qatar)AGAlexander GragerovOmeros Corporation (United States)OSOlga R. SlobodskayaLeiden University Medical Center

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Implication

Mechanistic study reveals HIV-1 Vpr activates viral and hormone-responsive promoters by binding p300/CBP, indicating Vpr functions as an adapter connecting transcription machinery.

Key Points

To determine the molecular mechanism by which the HIV-1 accessory protein Vpr activates transcription from viral and glucocorticoid-responsive promoters.
Assayed direct protein-protein interactions between Vpr and coactivators including p300/CBP, p/CAF, and p160 family members in vitro and in vivo.
Performed mutation and domain-mapping analyses to identify the specific contact sites mediating Vpr, p300, and glucocorticoid receptor interactions.
Conducted transcriptional competition assays using adenovirus E1A and truncated p300 fragments on MMTV and HIV-1 long terminal repeat promoters.
The C-terminus of Vpr bound directly to amino acids 2045–2191 of p300/CBP, overlapping the binding site for adenovirus E1A and p160 coactivators.
Vpr transactivation required the C-terminal transactivating region of p300 but functioned independently of its histone acetyltransferase enzymatic domain.
Coexpression of E1A or p300 interaction fragments inhibited Vpr transactivation, while Vpr mutants defective in glucocorticoid receptor binding displayed dominant-negative activity.

Cite This Study

Kino et al. (2002) studied this question.

synapsesocial.com/papers/6a9ac96ea5ca4dc838869b65 https://doi.org/10.1128/jvi.76.19.9724-9734.2002

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Implication

Mechanistic study reveals HIV-1 Vpr activates viral and hormone-responsive promoters by binding p300/CBP, indicating Vpr functions as an adapter connecting transcription machinery.

Human Immunodeficiency Virus Type 1 (HIV-1) Accessory Protein Vpr Induces Transcription of the HIV-1 and Glucocorticoid-Responsive Promoters by Binding Directly to p300/CBP Coactivators

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Key Points

Cite This Study

Human Immunodeficiency Virus Type 1 (HIV-1) Accessory Protein Vpr Induces Transcription of the HIV-1 and Glucocorticoid-Responsive Promoters by Binding Directly to p300/CBP Coactivators

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Key Points

Cite This Study

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