Transactivators
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In the context of gene regulation: transactivation is the increased rate of
gene expression Gene expression is the process (including its Regulation of gene expression, regulation) by which information from a gene is used in the synthesis of a functional gene product that enables it to produce end products, proteins or non-coding RNA, ...
triggered either by biological processes or by artificial means, through the expression of an intermediate transactivator protein. In the context of receptor signaling, transactivation occurs when one or more receptors activate yet another; receptor transactivation may result from the
crosstalk In electronics, crosstalk (XT) is a phenomenon by which a signal transmitted on one circuit or channel of a transmission system creates an undesired effect in another circuit or channel. Crosstalk is usually caused by undesired capacitive, ...
of
signaling cascade A biochemical cascade, also known as a signaling cascade or signaling pathway, is a series of chemical reactions that occur within a biological cell when initiated by a stimulus. This stimulus, known as a first messenger, acts on a receptor that ...
s or the activation of G protein–coupled receptor hetero-oligomer subunits, among other mechanisms.


Natural transactivation

Transactivation can be triggered either by endogenous cellular or viral proteins, also called transactivators. These protein factors act in trans (''i.e.'',
intermolecular An intermolecular force (IMF; also secondary force) is the force that mediates interaction between molecules, including the electromagnetic forces of attraction or repulsion which act between atoms and other types of neighbouring particles (e.g. ...
ly).
HIV The human immunodeficiency viruses (HIV) are two species of '' Lentivirus'' (a subgroup of retrovirus) that infect humans. Over time, they cause acquired immunodeficiency syndrome (AIDS), a condition in which progressive failure of the im ...
and
HTLV The primate T-lymphotropic viruses (PTLVs) are a group of retroviruses that infect primates, using their lymphocytes to reproduce. The ones that infect humans are known as human T-lymphotropic virus (HTLV), and the ones that infect Old World monk ...
are just two of the many viruses that encode transactivators to enhance viral gene expression. These transactivators can also be linked to cancer if they start interacting with, and increasing expression of, a cellular
proto-oncogene An oncogene is a gene that has the potential to cause cancer. In tumor cells, these genes are often mutated, or expressed at high levels.
. HTLV, for instance, has been associated with causing
leukemia Leukemia ( also spelled leukaemia; pronounced ) is a group of blood cancers that usually begin in the bone marrow and produce high numbers of abnormal blood cells. These blood cells are not fully developed and are called ''blasts'' or '' ...
primarily through this process. Its transactivator, ''Tax'''','' can interact with p40, inducing overexpression of
interleukin 2 Interleukin-2 (IL-2) is an interleukin, which is a type of cytokine signaling molecule forming part of the immune system. It is a 15.5–16 Dalton (unit), kDa protein that regulates the activities of white blood cells (leukocytes, often ...
,
interleukin receptor Interleukin receptors are a family of cytokine receptors for interleukins. They belong to the immunoglobulin superfamily. Types There are two main families of Interleukin receptors, Type 1 and Type 2. Type 1 Type 1 interleukin receptors incl ...
s, GM-CSF and the
transcription factor In molecular biology, a transcription factor (TF) (or sequence-specific DNA-binding factor) is a protein that controls the rate of transcription (genetics), transcription of genetics, genetic information from DNA to messenger RNA, by binding t ...
c-Fos Protein c-Fos is a proto-oncogene that is the human homolog of the retroviral oncogene v-fos. It is encoded in humans by the ''FOS'' gene. It was first discovered in rat fibroblasts as the transforming gene of the FBJ MSV (Finkel–Biskis–Ji ...
. HTLV infects
T-cell T cells (also known as T lymphocytes) are an important part of the immune system and play a central role in the adaptive immune response. T cells can be distinguished from other lymphocytes by the presence of a T-cell receptor (TCR) on their ce ...
s and via the increased expression of these stimulatory
cytokines Cytokines () are a broad and loose category of small proteins (~5–25 kDa) important in cell signaling. Cytokines are produced by a broad range of cells, including immune cells like macrophages, B cell, B lymphocytes, T cell, T lymphocytes ...
and
transcription factors In molecular biology, a transcription factor (TF) (or sequence-specific DNA-binding factor) is a protein that controls the rate of transcription of genetic information from DNA to messenger RNA, by binding to a specific DNA sequence. The fun ...
, leads to uncontrolled proliferation of T-cells and hence
lymphoma Lymphoma is a group of blood and lymph tumors that develop from lymphocytes (a type of white blood cell). The name typically refers to just the cancerous versions rather than all such tumours. Signs and symptoms may include enlarged lymph node ...
.


Artificial transactivation

Artificial transactivation of a gene is achieved by inserting it into the genome at the appropriate area as transactivator gene adjoined to special promoter regions of
DNA Deoxyribonucleic acid (; DNA) is a polymer composed of two polynucleotide chains that coil around each other to form a double helix. The polymer carries genetic instructions for the development, functioning, growth and reproduction of al ...
. The transactivator gene
expresses Expression may refer to: Linguistics * Expression (linguistics), a word, phrase, or sentence * Expression (mathematics), Symbolic description of a mathematical object * Fixed expression, a form of words with a specific meaning * Idiom, a type of ...
a transcription factor that binds to specific promoter region of DNA. By binding to the
promoter region In genetics, a promoter is a sequence of DNA to which proteins bind to initiate transcription of a single RNA transcript from the DNA downstream of the promoter. The RNA transcript may encode a protein (mRNA), or can have a function in and of it ...
of a gene, the transcription factor causes that gene to be expressed. The expression of one transactivator gene can activate multiple genes, as long as they have the same, specific promoter region attached. Because the expression of the transactivator gene can be controlled, transactivation can be used to turn genes on and off. If this specific promoter region is also attached to a
reporter gene Reporter genes are molecular tools widely used in molecular biology, genetics, and biotechnology to study gene function, expression patterns, and regulatory mechanisms. These genes encode proteins that produce easily detectable signals, such as ...
, we can measure when the transactivator is being expressed.


See also

*
Transrepression In the field of molecular biology, transrepression is a process whereby one protein represses (i.e., inhibits) the activity of a second protein through a protein-protein interaction. Since this repression occurs between two different protein molecu ...
*
Selective glucocorticoid receptor agonist Selective glucocorticoid receptor modulators (SEGRMs) and selective glucocorticoid receptor agonists (SEGRAs) formerly known as dissociated glucocorticoid receptor agonists (DIGRAs) are a class of experimental drugs designed to share many of th ...


References


External links

* {{MeshName, Transactivators Molecular biology