Nuclear translocation of an exogenous fusion protein containing HIV Tat requires unfolding

@article{Bonifaci1995NuclearTO,
  title={Nuclear translocation of an exogenous fusion protein containing HIV Tat requires unfolding},
  author={Neris Bonifaci and Roberto Sitia and Anna Rubartelli},
  journal={AIDS},
  year={1995},
  volume={9},
  pages={995–1000}
}
ObjectiveTo characterize the transcellular transport of HIV-1 Tat. HIV-1 Tat contains a putative localization signal and no leader peptide; however, it can be released from virus-infected cells and taken up by uninfected cells. Design and methodsWe constructed a chimeric protein between Tat and dihydrofolate reductase (DHFR), a cytosolic enzyme that binds tightly to the folate analogue methotrexate (MTX). As confirmed by protease sensitivity assays, binding to MTX results in stabilization of… Expand
Transcellular protein transduction using the Tat protein of HIV-1.
TLDR
The Tat protein of HIV-1 is a powerful transactivator of gene expression that interacts with a structured RNA sequence at the 5' end of the viral mRNA, and mediates their efficient cellular internalization and can be thus utilized for transcellular protein transduction. Expand
Caveolae-mediated internalization of extracellular HIV-1 tat fusion proteins visualized in real time.
TLDR
It is demonstrated that the internalization process of full-length Tat and of heterologous proteins fused to the transduction domain of Tat exploits a caveolar-mediated pathway and is inhibited at 4 degrees C. Expand
Exosome-associated release, uptake, and neurotoxicity of HIV-1 Tat protein
TLDR
Results show a significant fraction of Tat is secreted and present in the form of exosomes and may contribute to the stability of extracellular Tat and broaden the spectrum of its target cells. Expand
The Association of HIV-1 Tat with Nuclei Is Regulated by Ca2+ Ions and Cytosolic Factors*
TLDR
It is shown that cytosolic components activated by Ca2+ ions are required to reveal the karyophilic properties of Tat: in vitro translated Tat molecules do not associate with isolated nuclei unless preincubated with Ca2+. Expand
Intracellular delivery of a Tat-eGFP fusion protein into muscle cells.
TLDR
Muscles injected with Tat-eGFP showed intense labeling of the extracellular matrix (ECM), suggesting that, although Tat fusion proteins can transduce muscle fibers, their binding by components of the ECM surrounding myofibers could interfere with the intracellular transduction process. Expand
HIV-1 Vpr displays natural protein-transducing properties: implications for viral pathogenesis.
TLDR
Effective transduction of biologically active, synthetic Vpr (sVpr) as well as the Vpr-beta-galactosidase fusion protein is demonstrated. Expand
HIV-1 Tat enters T cells using coated pits before translocating from acidified endosomes and eliciting biological responses.
TLDR
HIV-1 Tat enters T cells essentially like diphtheria toxin, using clathrin-mediated endocytosis before low-pH-induced and Hsp90-assisted endosomal translocation, indicating that cytosolic delivery is required for Tat signaling. Expand
Cyclophilin A enables specific HIV-1 Tat palmitoylation and accumulation in uninfected cells
TLDR
In uninfected cells, incoming HIV-1 Tat is palmitoylated on Cys31 by DHHC-20, which increases its affinity for PI(4,5)P2 and results in its accumulation at the plasma membrane. Expand
Molecular determinants for cellular uptake of Tat protein of human immunodeficiency virus type 1 in brain cells
TLDR
It is demonstrated that 125I-Tat uptake could be inhibited by dextran sulfate and competitively inhibited by unlabeled Tat but not by overlapping 15-mer peptides, suggesting that Tat internalization is charge and conformationally dependent. Expand
Mutational analysis of a human immunodeficiency virus type 1 Tat protein transduction domain which is required for delivery of an exogenous protein into mammalian cells.
TLDR
The modified PTD sequences designed in this study may provide useful tools necessary for delivering therapeutic proteins/peptides into cells and facilitate the simple and specific identification of protein transduction mediated by these peptide sequences. Expand
...
1
2
3
4
5
...