Tat is an HIV

HIV

Human immunodeficiency virus is a lentivirus that causes acquired immunodeficiency syndrome , a condition in humans in which progressive failure of the immune system allows life-threatening opportunistic infections and cancers to thrive...

 gene.

Tat stands for "Trans-Activator of Transcription

Transcription (genetics)

Transcription is the process of creating a complementary RNA copy of a sequence of DNA. Both RNA and DNA are nucleic acids, which use base pairs of nucleotides as a complementary language that can be converted back and forth from DNA to RNA by the action of the correct enzymes...

". Tat consists of between 86 and 101 amino acids depending on the subtype.

Function

Tat vastly increases the level of transcription of the HIV

HIV

Human immunodeficiency virus is a lentivirus that causes acquired immunodeficiency syndrome , a condition in humans in which progressive failure of the immune system allows life-threatening opportunistic infections and cancers to thrive...

 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

Positive feedback

Positive feedback is a process in which the effects of a small disturbance on a system include an increase in the magnitude of the perturbation. That is, A produces more of B which in turn produces more of A. In contrast, a system that responds to a perturbation in a way that reduces its effect is...

 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

Toxin

A toxin is a poisonous substance produced within living cells or organisms; man-made substances created by artificial processes are thus excluded...

 producing cell death via apoptosis

Apoptosis

Apoptosis is the process of programmed cell death that may occur in multicellular organisms. Biochemical events lead to characteristic cell changes and death. These changes include blebbing, cell shrinkage, nuclear fragmentation, chromatin condensation, and chromosomal DNA fragmentation...

 in uninfected "bystander" T cell

T cell

T cells or T lymphocytes belong to a group of white blood cells known as lymphocytes, and play a central role in cell-mediated immunity. They can be distinguished from other lymphocytes, such as B cells and natural killer cells , by the presence of a T cell receptor on the cell surface. They are...

s, assisting in progression toward AIDS

AIDS

Acquired immune deficiency syndrome or acquired immunodeficiency syndrome is a disease of the human immune system caused by the human immunodeficiency virus...

.

By interacting with the CXCR4

CXCR4

C-X-C chemokine receptor type 4 also known as fusin or CD184 is a protein that in humans is encoded by the CXCR4 gene.- Function :...

 receptor, Tat also appears to encourage the reproduction of less virulent M-tropic (macrophage

Macrophage

Macrophages are cells produced by the differentiation of monocytes in tissues. Human macrophages are about in diameter. Monocytes and macrophages are phagocytes. Macrophages function in both non-specific defense as well as help initiate specific defense mechanisms of vertebrate animals...

-tropic) strains of HIV (which use the CCR5

CCR5

C-C chemokine receptor type 5, also known as CCR5, is a protein that in humans is encoded by the CCR5 gene. CCR5 is a member of the beta chemokine receptors family of integral membrane proteins...

 receptor) early in the course of infection, allowing the more rapidly pathogenic T-tropic (T-cell-tropic) strains (which use the CXCR4

CXCR4

C-X-C chemokine receptor type 4 also known as fusin or CD184 is a protein that in humans is encoded by the CXCR4 gene.- Function :...

 receptor) to emerge later.

Protein transduction domain

Tat contains a protein transduction domain, and is therefore known as a cell penetrating peptide

Cell penetrating peptide

Cell-penetrating peptides are short peptides that facilitate cellular uptake of various molecular cargo . The "cargo" is associated with the peptides either through chemical linkage via covalent bonds or through non-covalent interactions...

. Originally characterised by Frankel and Pabo (1988) and Green and Loewenstein (1988), this domain allows Tat to enter cells by crossing the cell membrane

Cell membrane

The cell membrane or plasma membrane is a biological membrane that separates the interior of all cells from the outside environment. The cell membrane is selectively permeable to ions and organic molecules and controls the movement of substances in and out of cells. It basically protects the cell...

. 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.