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HMGB1
High mobility group box 1 protein, 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 the high mobility group and contains a HMG-box domain.
Like the histones, HMGB1 is among the most important chromatin proteins. In the nucleus HMGB1 interacts with nucleosomes, transcription factors, and histones. This nuclear protein organizes the DNA and regulates transcription. After binding, HMGB1 bends DNA, which facilitates the binding of other proteins. HMGB1 supports transcription of many genes in interactions with many transcription factors. It also interacts with nucleosomes to loosen packed DNA and remodel the chromatin. Contact with core histones changes the structure of nucleosomes.
The presence of HMGB1 in the nucleus depends on posttranslational modifications. When the protein is not acetylated, it stays in the nucleus, but hyperacetylation on lysine residues causes it to translocate into the cytosol.
HMGB1 has been shown to play an important role in helping the RAG endonuclease form a paired complex during V(D)J recombination.
HMGB1 is secreted by immune cells (e.g. macrophages, monocytes and dendritic cells) through leaderless secretory pathway. Activated macrophages and monocytes secrete HMGB1 as a cytokine mediator of inflammation. Antibodies that neutralize HMGB1 confer protection against damage and tissue injury during arthritis, colitis, ischemia, sepsis, endotoxemia, and systemic lupus erythematosus.[citation needed] The mechanism of inflammation and damage consists of binding to toll-like receptor TLR2 and TLR4, which mediates HMGB1-dependent activation of macrophage cytokine release. This positions HMGB1 at the intersection of sterile and infectious inflammatory responses.
ADP-ribosylation of HMGB1 by PARP1 inhibits removal of apoptotic cells, thereby sustaining inflammation. TLR4 binding by HMGB1 or lipopolysaccharide (LPS) sustains ADP-ribosylation of HMGB1 by PARP1 thereby serving as an amplification loop for inflammation.
HMGB1 has been proposed as a DNA vaccine adjuvant. HMGB1 released from tumour cells was demonstrated to mediate anti-tumour immune responses by activating toll-like receptor 2 (TLR2) signaling on bone marrow-derived GBM-infiltrating DCs.
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HMGB1
High mobility group box 1 protein, 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 the high mobility group and contains a HMG-box domain.
Like the histones, HMGB1 is among the most important chromatin proteins. In the nucleus HMGB1 interacts with nucleosomes, transcription factors, and histones. This nuclear protein organizes the DNA and regulates transcription. After binding, HMGB1 bends DNA, which facilitates the binding of other proteins. HMGB1 supports transcription of many genes in interactions with many transcription factors. It also interacts with nucleosomes to loosen packed DNA and remodel the chromatin. Contact with core histones changes the structure of nucleosomes.
The presence of HMGB1 in the nucleus depends on posttranslational modifications. When the protein is not acetylated, it stays in the nucleus, but hyperacetylation on lysine residues causes it to translocate into the cytosol.
HMGB1 has been shown to play an important role in helping the RAG endonuclease form a paired complex during V(D)J recombination.
HMGB1 is secreted by immune cells (e.g. macrophages, monocytes and dendritic cells) through leaderless secretory pathway. Activated macrophages and monocytes secrete HMGB1 as a cytokine mediator of inflammation. Antibodies that neutralize HMGB1 confer protection against damage and tissue injury during arthritis, colitis, ischemia, sepsis, endotoxemia, and systemic lupus erythematosus.[citation needed] The mechanism of inflammation and damage consists of binding to toll-like receptor TLR2 and TLR4, which mediates HMGB1-dependent activation of macrophage cytokine release. This positions HMGB1 at the intersection of sterile and infectious inflammatory responses.
ADP-ribosylation of HMGB1 by PARP1 inhibits removal of apoptotic cells, thereby sustaining inflammation. TLR4 binding by HMGB1 or lipopolysaccharide (LPS) sustains ADP-ribosylation of HMGB1 by PARP1 thereby serving as an amplification loop for inflammation.
HMGB1 has been proposed as a DNA vaccine adjuvant. HMGB1 released from tumour cells was demonstrated to mediate anti-tumour immune responses by activating toll-like receptor 2 (TLR2) signaling on bone marrow-derived GBM-infiltrating DCs.