HMGB1
Encyclopedia
High-mobility group protein B1, also known as high-mobility group protein 1 (HMG-1) and amphoterin, is a protein
that in humans is encoded by the HMGB1 gene
.
HMG-1 belongs to high mobility group
.
mediator of Inflammation
. Antibodies that neutralize HMGB1 confer protection against damage and tissue injury during arthritis
, colitis
, ischemia
, sepsis
, endotoxemia, and systemic lupus erythematosis. The mechanism of inflammation and damage is binding to TLR4, which mediates HMGB1-dependent activation of macrophage cytokine release. This positions HMGB1 at the intersection of sterile and infectious inflammatory responses.
HMGB1 has been studied as a DNA vaccine adjuvant
.
with P53
.
HMGB1 is an intracellular protein that can translocate to the nucleus where it binds DNA and regulates gene expression. It can also be released from cells, in which extracellular form it can bind the inflammatory receptor RAGE (Receptor for Advanced Glycan Endproducts]. Release from cells seems to involve two distinct processes: necrosis, in which case cell membranes are permeabilized and intracellular constitutents may diffuse out of the cell; and some form of active or facilitated secretion induced by signaling through the NFkappaB.
HMGB1 can interact with TLR ligands and cytokines, and activates cells through the multiple surface receptors including TLR2, TLR4, and RAGE.
Cancer therapy :
HMGB1 has been proposed as a target for cancer therapy.
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
that in humans is encoded by the HMGB1 gene
Gene
A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...
.
HMG-1 belongs to high mobility group
High mobility group
High-Mobility Group or HMG is a group of chromosomal proteins that help withtranscription, replication, recombination, and DNA repair.-Families:The HMG proteins are subdivided into 3 superfamilies each containing a characteristic functional domain:...
.
Role in Inflammation
Activated macrophages and monocytes secrete HMGB1 as a cytokineCytokine
Cytokines are small cell-signaling protein molecules that are secreted by the glial cells of the nervous system and by numerous cells of the immune system and are a category of signaling molecules used extensively in intercellular communication...
mediator of Inflammation
Inflammation
Inflammation is part of the complex biological response of vascular tissues to harmful stimuli, such as pathogens, damaged cells, or irritants. Inflammation is a protective attempt by the organism to remove the injurious stimuli and to initiate the healing process...
. Antibodies that neutralize HMGB1 confer protection against damage and tissue injury during arthritis
Arthritis
Arthritis is a form of joint disorder that involves inflammation of one or more joints....
, colitis
Colitis
In medicine, colitis refers to an inflammation of the colon and is often used to describe an inflammation of the large intestine .Colitides may be acute and self-limited or chronic, i.e...
, ischemia
Ischemia
In medicine, ischemia is a restriction in blood supply, generally due to factors in the blood vessels, with resultant damage or dysfunction of tissue. It may also be spelled ischaemia or ischæmia...
, sepsis
Sepsis
Sepsis is a potentially deadly medical condition that is characterized by a whole-body inflammatory state and the presence of a known or suspected infection. The body may develop this inflammatory response by the immune system to microbes in the blood, urine, lungs, skin, or other tissues...
, endotoxemia, and systemic lupus erythematosis. The mechanism of inflammation and damage is binding to TLR4, which mediates HMGB1-dependent activation of macrophage cytokine release. This positions HMGB1 at the intersection of sterile and infectious inflammatory responses.
HMGB1 has been studied as a DNA vaccine adjuvant
Adjuvant
An adjuvant is a pharmacological or immunological agent that modifies the effect of other agents, such as a drug or vaccine, while having few if any direct effects when given by itself...
.
Interactions
HMGB1 has been shown to interactProtein-protein interaction
Protein–protein interactions occur when two or more proteins bind together, often to carry out their biological function. Many of the most important molecular processes in the cell such as DNA replication are carried out by large molecular machines that are built from a large number of protein...
with P53
P53
p53 , is a tumor suppressor protein that in humans is encoded by the TP53 gene. p53 is crucial in multicellular organisms, where it regulates the cell cycle and, thus, functions as a tumor suppressor that is involved in preventing cancer...
.
HMGB1 is an intracellular protein that can translocate to the nucleus where it binds DNA and regulates gene expression. It can also be released from cells, in which extracellular form it can bind the inflammatory receptor RAGE (Receptor for Advanced Glycan Endproducts]. Release from cells seems to involve two distinct processes: necrosis, in which case cell membranes are permeabilized and intracellular constitutents may diffuse out of the cell; and some form of active or facilitated secretion induced by signaling through the NFkappaB.
HMGB1 can interact with TLR ligands and cytokines, and activates cells through the multiple surface receptors including TLR2, TLR4, and RAGE.
Cancer therapy :
HMGB1 has been proposed as a target for cancer therapy.