Tat (HIV)



Tat is a HIV gene.

Tat stands for "Trans-Activator of Transcription". Tat consists of between 86 and 101 amino acids depending on the subtype.

Function
Tat vastly increases the level of transcription of the HIV dsRNA. Before Tat is present, a small number of RNA transcripts will be made, which allow the Tat protein to be produced. Tat then binds to cellular factors and mediates their phosphorylation, resulting in increased transcription of all HIV genes, providing a positive feedback cycle. This in turn allows HIV to have an explosive response once a threshold amount of Tat is produced, a useful tool for defeating the body's response.

Tat also appears to play a more direct role in the HIV disease process. The protein is released by infected cells in culture, and is found in the blood of HIV-1 infected patients.

It can be absorbed by cells that are not infected with HIV, and can act directly as a toxin producing cell death via apoptosis in uninfected "bystander" T cells, assisting in progression toward AIDS.

By interacting with the CXCR4 receptor, Tat also appears to encourage the reproduction of less virulent M-tropic strains of HIV early in the course of infection, allowing the more rapidly pathogenic T-tropic strains to emerge later.

Protein transduction domain
Tat contains a protein transduction domain, and is therefore known as a cell penetrating peptide. Originally characterised by Frankel and Pabo (1988) and Green and Loewenstein (1988), this domain allows Tat to enter cells by crossing the cell membrane. The nuclear localisation signal found within the domain, GRKKR, mediates further translocation of Tat into the cell nucleus. The biological role of this domain and exact mechanism of transfer is unknown. The amino acid sequence of the protein transduction domain is YGRKKRRQRRR.

Clinical significance
Inhibition of Tat has been investigated. It has been suggested that Tat antagonists may be of use in the treatment of HIV infections. TAT's Protein Transduction Domain has also been used in protein fusion studies to aid in the transduction of proteins as a delivery method for protein therapeutics.