HMGB2

What is HMGB2 Protein?

HMGB2 is a protein found widely in the nuclei of higher eukaryotic cells. It’s known for bending DNA and aiding in effective DNA loop formation, which enhances DNA flexibility and the interaction between proteins. This protein also plays a role in the last step of DNA double-strand break repair and V(D)J recombination. It shows variable expression levels across different tissues, being notably abundant in bone marrow and lymph nodes. Abnormal HMGB2 levels are linked with diseases like juvenile rheumatoid arthritis and autoimmune hepatitis. In the cancer realm, increased HMGB2 expression is tied to tumor development and poor prognosis. Thus, HMGB2 is crucial for gene transcription regulation, recombination, and repair, and serves as a potential biomarker and therapeutic target in various diseases.

What is the Function of HMGB2 Protein?

HMGB2, or High Mobility Group Box 2 protein, plays multiple roles in the nucleus, influencing DNA transcription, replication, and recombination. Its ability to bind DNA allows it to act in chromatin remodeling and as a molecular chaperone in DNA-dependent processes. HMGB2 can bind to various DNA structures, including supercoiled plasmid DNA and cisplatin-modified DNA, causing DNA bending. This binding angle can range from 30 to 130°, typically around 70 to 90° for single-domain HMGB proteins. Moreover, its extensive protein-protein interaction network affects its functions both inside and outside the nucleus. Increased HMGB2 expression is linked to several pathological processes like tumor progression, aiding in cancer cell proliferation, glycolysis, invasion, and metastasis, and correlates with tumor size, invasiveness, stage development, and sensitivity to drugs like cisplatin. Hence, HMGB2 is crucial in gene transcription regulation, DNA repair, recombination, and the development of diseases.

HMGB2 Related Signaling Pathway

HMGB2 plays versatile roles in cellular signaling pathways, mainly in gene regulation, DNA repair, tumor progression, cell aging, immune response, chromatin remodeling, and hormone receptor signaling. As a DNA chaperone, it influences gene expression through interactions with DNA and chromatin, especially under cisplatin treatment. It affects the proliferation and metastasis of tumor cells by impacting Wnt/β-catenin and AKT pathways. HMGB2 also regulates SASP gene expression in aging and acts as a DAMP molecule in inflammatory and immune responses. Additionally, it interacts with CTCF to influence 3D gene structures and with steroid hormone receptors to boost their transcriptional activity, underscoring its key role in genome stability, DNA repair, immune modulation, and cancer development.

HMGB2 Related Diseases

HMGB2 protein is tied to many diseases and stands out more and more in how it works in these conditions. It’s linked to cancer by pushing tumor growth, invasion, and spread. In heart-related diseases, researchers are starting to understand its role, opening doors to new prevention and treatment ideas. HMGB2 also shows up in autoimmune diseases like juvenile rheumatoid arthritis and autoimmune hepatitis. It might even be a marker for diagnosing and treating liver fibrosis and cirrhosis. In pulmonary hypertension, this protein plays a crucial role in how lung vessels change and can help predict patient risk. It’s also connected to coronary artery calcification and might relate to chronic inflammatory conditions like diabetes, lung, and kidney issues. So, HMGB2 is a big player in various health problems, and diving deeper into its role could change how we tackle these diseases.

Bioapplications of HMGB2

Recombinant HMGB2 protein finds its use in research, industrial, and medical fields. In research, it’s essential for studying transcription, chromatin remodeling, and V(D)J recombination. It’s used to simulate and understand DNA binding and its effects in the nucleus. Industry-wise, it helps in creating specific antibodies, diagnostic tools, and serves as a target for drug screening. Medically, HMGB2 is linked to the development of cancers, cardiovascular diseases, and autoimmune conditions, making it vital for exploring these diseases at a molecular level and crafting new treatments. Its potential as a drug target and biomarker in cancer diagnosis and therapy is also being explored. Thus, recombinant HMGB2 is key in advancing research and creating diagnostic and therapeutic strategies.

Case Study 1: Zheng Y. et al. Atherosclerosis. 2024

Aortic dissection (AD) is a deadly condition that’s tough to crack. HMGB2, from the high mobility group protein family, is tied to immune and inflammatory diseases, but its AD role is murky. In mice without HMGB2, researchers used β-aminopropionitrile and Ang II to mimic AD. They overexpressed HMGB2 in some mice using AAV9-HMGB2. They then checked out aorta changes through several staining methods and measured HMGB2 levels. High HMGB2 was seen in AD patients and mouse models, spurring cell growth and moving GLUT4 around while lowering GLUT1. It also blocked SIRT1/PGC-1α, reversible by hindering PPAR-γ. Interestingly, lacking HMGB2 lowered AD rates, but boosting it made things worse.

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  Fig1. A study using the signaling inhibitor ICG001 demonstrated the role of the Wnt/β-catenin pathway in the upregulation of HMGB2 and LEF1.
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  Fig2. Changes in GLUT1 and GLUT4 protein levels in cells with HMGB2 knockdown.

Case Study 2: Kong D. et al. Arterioscler Thromb Vasc Biol. 2024

Pulmonary hypertension (PH) is a deadly disease marked by abnormal growth and resistance to cell death in pulmonary artery smooth muscle cells (PASMCs), similar to cancer traits. While HMGB2 protein is known for promoting cell growth and survival in cancer, its role in PH was previously unknown. Studies involving mice and rats with altered HMGB2 expression have shown that reducing HMGB2 can lessen PH development, while its overexpression worsens the condition. HMGB2 encourages PASMC proliferation via certain signaling pathways, and higher HMGB2 levels in patients correlate with more severe PH and predict poorer outcomes.

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  Fig3. Immunoblots and quantification of hPASMCs treated with indicated concentrations of HMGB2.
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  Fig4. Representative fluorescence microscopic images of 5-ethynyl-2′-deoxyuridine (EdU)-positive cells.

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  Fig1. HMGB2 is a risk factor and new preventive target for AD. (Yameng Zheng, 2024)
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  Fig2. Functional and physical interactions between HMGB2, RUNX2, and LEF1 on a promoter containing a TCF/ LEF motif. (Noboru Taniguchi, 2018)

HMGB2 has several biochemical functions, for example, DNA binding,DNA binding, bending,RAGE receptor binding. Some of the functions are cooperated with other proteins, some of the functions could acted by HMGB2 itself. We selected most functions HMGB2 had, and list some proteins which have the same functions with HMGB2. You can find most of the proteins on our site.

Function	Related Protein
supercoiled DNA binding	RPS3,HMGB1,PSIP1
enhancer sequence-specific DNA binding	ATF2,MYT1,XBP1,TFAP2B,ISL1,TBX19,SOX9,KLF7B,FOXN4,LDB1
damaged DNA binding	NEIL1,RPS3,POLK,TDG,RAD23B,NEIL2,RAD52,DCLRE1C,RAD23A,REV1
four-way junction DNA binding	RAD51L3,MEN1,HMGB3,DMC1,RAD51,YY1,RAD51L1,HMGB1
double-stranded DNA binding	MTERFD2,RAD51D,HMGB1,XRCC6,NKX2-8,XRCC2,TDP1,NEIL3,DDX58,GTF2H4
poly(A) RNA binding	RPS27L,UBFD1,ZNF638,RPS4Y1,EXOSC8,DIDO1,SNRPG,FXR2,SRP54A,ZRANB2
chromatin binding	ATAD2,SIRT2,HMGA1,SUZ12,RUNX2,HDAC7A,TSHZ3,SVEP1,BAZ1B,RCC1
RAGE receptor binding	S100A4,S100P,S100B,S100A7,FPR1,S100A8,HMGB1,S100A9,S100A12,S100A13
single-stranded DNA binding	RAD51,PCBP1,MEIOB,HNRNPA1,RAD23B,PURB,SSBP2,RAD51B,RPA2,RAD23A

HMGB2 has direct interactions with proteins and molecules. Those interactions were detected by several methods such as yeast two hybrid, co-IP, pull-down and so on. We selected proteins and molecules interacted with HMGB2 here. Most of them are supplied by our site. Hope this information will be useful for your research of HMGB2.

PKNOX1;CSNK1A1;4505953;EIF1B;NFKB1;TRAF6;q81k61_bacan;mdm2_human_probe