This website uses cookies to ensure you get the best experience on our website.
- Table of Contents
11 Citations 17 Q&As
5 Citations 16 Q&As
7 Citations 5 Q&As
Facts about High mobility group protein B1.
Proposed to be an universal biosensor for nucleic acids. Promotes host inflammatory response to sterile and infectious signals and is included in the coordination and integration of both innate and adaptive immune responses.
Human | |
---|---|
Gene Name: | HMGB1 |
Uniprot: | P09429 |
Entrez: | 3146 |
Belongs to: |
---|
HMGB family |
Amphoterin; high mobility group box 1; High mobility group protein 1; high mobility group protein B1; high-mobility group (nonhistone chromosomal) protein 1; high-mobility group box 1; HMG1; HMG-1; HMG1DKFZp686A04236; HMG3; HMGB1; SBP-1; Sulfoglucuronyl carbohydrate binding protein
Mass (kDA):
24.894 kDA
Human | |
---|---|
Location: | 13q12.3 |
Sequence: | 13; NC_000013.11 (30456704..30617597, complement) |
Ubiquituous. Expressed in platelets (PubMed:11154118).
Nucleus. Chromosome. Cytoplasm. Secreted. Cell membrane; Peripheral membrane protein; Extracellular side. Endosome. Endoplasmic reticulum-Golgi intermediate compartment. In basal state predominantly nuclear. Shuttles between the cytoplasm and the nucleus (PubMed:12231511, PubMed:17114460). Translocates from the nucleus to the cytoplasm upon autophagy stimulation (PubMed:20819940). Release from macrophages in the extracellular milieu requires the activation of NLRC4 or NLRP3 inflammasomes (By similarity). Passively released to the extracellular milieu from necrotic cells by diffusion, involving
The HMGB1 marker is among the most suitable DAMP molecules to study osteosarcoma. This molecule regulates gene transcription, which means it could be used to determine osteosarcoma development. But how do you know whether this molecule is a good candidate for research on osteosarcoma? Continue reading to find out more!
HMGB1 is multifunctional protein that performs different roles within the human body. It is a major mediator in lethal inflammation. This makes it a popular target for the development of new drugs and research. HMGB1 is implicated in many human diseases like asthma and respiratory infections. It's therefore a promising target for immunotherapy. Listed below are some of its roles.
HMGB1 is a protein containing 215 amino acids. It is made up of two DNA binding motifs, box A and B, and two nuclear localization sequences. The HMGB1 protein acts as a DAMP molecule, inhibiting cytokine activity and regulating the matrix. Three cysteines in HMGB1 are necessary for the anti-inflammatory action. Despite these properties, HMGB1 remains an intriguing option for immunotherapy.
HMGB1 sends signals to multiple receptors. HMGB1 communicates with eleven receptors currently. Recent findings on the function and biology of TLR4 can be useful in understanding HMGB1 biology. Interestingly, HMGB1 also inhibits NOS3 expression within macrophages, as well as NOS2 mRNA. HMGB1 also blocks NOS2 Kinase activity and blocks immunosuppressive effects on mesenchymal-derived stem cells.
Since its discovery , 16 years ago, HMGB1 research has increased exponentially. From 281 reports in 1995 to 2,261 during 2009-2014, there were many studies on the advancements in HMGB1 biology. HMGB1 has been identified as an DAMP and a sporadic danger indicator in the immune system as well as other organs. However, it's not only the biology of HMGB1 that needs to be better comprehended.
HMGB1 can stimulate TLR4 by regulating the activity of the PKC receptor. CXCL12 can be activated by HMGB1, but its main function is activating TLR4 through the CXCR4 pathway. It is not known what mechanism activates HMGB1. However, HMGB1 has been shown to be involved in the control and maintenance of inflammation in cancer cells. And the role of calcium ions in HMGB1 is undisputed.
Extracellular HMGB1 was extensively studied in mice suffering from gramnegative bacteria severe sepsis. This model is induced by cecal puncture and ligation. Neutralizing monoclonal antibodies against HMGB1 help to reduce tissue injury and decrease lethality. Furthermore, siRNA-specific knockdown of HMGB1 suppresses cytokine production and saves mice that have been hybridized.
Anti-HMGB1 binding m2G7 bonds box A within HMGB1 to hinder interactions between HMGB1 (TLR4 and RAGE). Anti-HMGB1 m2G7 can be used to treat a variety of inflammatory diseases. Its antagonists inhibit RAGE-mediated endocytosis. They also block RAGE binding to HMGB1.
A study from a lab in Germany found that human tendon-derived tissues from six patients suffering from early tendinopathy were significantly higher in HMGB1 than in the control group. These results were not correlated with the age of the patient or the frequency of injections of steroids. The results also revealed that HMGB1 was expressed primarily in stromal cells of the extracellular matrix, in contrast to 5 percent of immune cells. CD45 staining with immunofluorescence revealed that HMGB1 was expressed predominantly by stromal cells but not by immune cells. It is interesting to note that TLR4 expression in cancer cells was linked to an increase in HMGB1 levels.
While the function of HMGB1 has been in debate for a long time, it was recently discovered that the protein is responsible for regulating gene transcription in mesenchymal stem cells. In this study, the researchers utilized mesenchymal stem cells taken from human bone marrow to determine HMGB1. These cells moved into a solution that contained purified HMGB1, then into a neutral solution that contained an anti-HMGB1 polyclonal antibody.
In addition to regulating gene expression, HMGB1 also binds to TLR4 on the cell's surface, which is a receptor for NF-kBthat is responsible for the development of cancer metastasis. The presence of CAFs enhances TLR4 expression by increasing p65 and IkBa phosphorylation. The expression of p65 and IkBa as a signpost of activation of the NF-kB receptor, increases after CAF stimulation.
Researchers have discovered that HMGB1 increased the expression of NFs as well as CAFs. Both types of cells release HMGB1 at a similar rate however, the percentage released by CAF cells is greater than that of NFs. Nevertheless, both types of cells express HMGB1 to a much greater extent than lung cancer cells. This is in line with a prior study that discovered HMGB1 regulates the transcription of genes in cancer cell.
The expression of HMGB proteins is widely used in cell biology. To introduce genes using viral vectors. Adenoviruses are a good example. are used to introduce genes into cells. The proteins that these viruses make are expressed on the cells targeted by the virus. HMGB1 has been found in lung cancer cells that promote metastasis. This study could shed some information on the role played by these proteins and cancer.
It was found that CAFs treated for 24 hours with recombinant HMGB1 show the genes that are corresponding to them. This suggests that HMGB1 can slow the growth of cancer. The cells were then subjected western blotting. After 24 hours, the proteins were expressed as expected and the levels that corresponded were measured using ELISA. The study was conducted using various methods, and is in line with previous studies.
This study also demonstrates that HMGB1 promotes the growth of prostate cancer cells. It has been demonstrated that HMGB1 activates Akt signaling pathways, and also facilitates expression of Brahma related gene 1 in colorectal cancer cells. These proteins also can activate the HMGB1 pathway or RAGE to promote the growth and motility of colorectal cancer cells.
While there isn't much data regarding the role of HMGB1's prognostic function in osteosarcomas, previous studies have proven that it is associated with lower overall survival. Additionally, higher HMGB1 expression was associated with lower recurrence-free survival rates. HMGB1 has also been proven to be a significant marker of TNM stage and tumor size as well as tumor size, which are two of the most known prognostic factors for osteosarcoma. In addition, age was not an independent factor.
The immunoreactivity of HMGB1 has been found to be restricted to tubular and cytoplasmic epitheliums in osteosarcoma. A higher staining level was associated with a higher differentiation grade of the tumor. This study strongly suggests that HMGB1 could be a marker for osteosarcoma Recurrence.
To identify osteosarcoma biomarkers GSE39055 gene expression data was used. The modules were compared, and a median risk score was calculated. Both groups also had different expression levels of certain genes. The high-risk group was less likely to develop osteosarcoma when compared to the low-risk. These genes were tested in a Cox regression model, which determined their predictive capacity.
HMGB1 can be found in osteosarcoma cell membrane cells. It has been established that its expression in this tissue is significantly linked to survival and metastases. These studies are crucial to osteosarcoma diagnosis and treatment. However, the research needs to be further developed. This is a research endeavor that will study the possible significance of HMGB1 as a biomarker to detect osteosarcoma-related recurrence in osteosarcoma.
HMGB1 is an atomic protein that travels between the nucleus and the cytoplasm. It is composed of two putative nuclear export signals (NLSs) that interact with the nuclear transport receptor CRM-1. These NLSs contain conserved lysine lysine residues and are sensitive to acetylation. Acetylation can activate nuclear exclusion or translocation. HMGB1 is subject to extensive post-translational modifications and is controlled by numerous proteins.
HMGB1 plays a role in the regulation of cell death via blocking RAGE. Osteosarcoma therapy could involve the inhibition of RAGE activity. Its inhibition causes caspase activity to be slowed which increases the possibility of repeat incidence. The efficacy of chemotherapy drugs like bortezomib might be enhanced by inhibiting HMGB1.
Researchers have discovered that HMGB1-related upregulation is associated with increased autophagy levels in human myeloid cells. This has implications for osteosarcoma treatment and development of drugs. In addition to this, HMGB1 downregulation can also hinder autophagy, a crucial process in cancer treatment. HMGB1 is involved in a myriad of cell processes, including differentiation, and blocks autophagy.
PMID: 2922262 by Wen L., et al. A human placental cDNA clone that encodes nonhistone chromosomal protein HMG-1.
PMID: 8661151 by Ferrari S., et al. The active gene that encodes human high mobility group 1 protein (HMG1) contains introns and maps to chromosome 13.
*More publications can be found for each product on its corresponding product page