The human HMGB1 promoter is modulated by a silencer and an enhancer-containing intron

Lum, H.K.; Lee, Kam-Len Daniel

doi:10.1016/s0167-4781(01)00243-3

Cited by 23 publications

(29 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Expression of another RAGE ligand, S100A9, was associated with poor differentiation in breast cancer tissues [81]. High levels of HMGB1 have also been observed in human primary breast carcinoma [82], and this expression was further enhanced by estrogen [34,83]. Taken together, there is considerable evidence for the importance of RAGE ligands in breast cancer; however, it is currently unclear which of these effects are mediated by RAGE.…”

Section: Breast Cancermentioning

confidence: 99%

RAGE and RAGE Ligands in Cancer

Logsdon

Fuentes

Huang

et al. 2007

CMM

187

170

View full text Add to dashboard Cite

The receptor for advanced glycation end-products (RAGE) is a multifunctional receptor with multiple ligands that is known to play a key role in several diseases, including diabetes, arthritis, and Alzheimer's disease. Recent evidence indicates that this receptor also has an important role in cancer. RAGE ligands, which include the S100/calgranulins and high-mobility group box 1 (HMGB1) ligands, are expressed and secreted by cancer cells and are associated with increased metastasis and poorer outcomes in a wide variety of tumors. These ligands can interact in an autocrine manner to directly activate cancer cells and stimulate proliferation, invasion, chemoresistance, and metastasis. RAGE ligands derived from cancer cells can also influence a variety of important cell types within the tumor microenvironment, including fibroblasts, leukocytes, and vascular cells, leading to increased fibrosis, inflammation, and angiogenesis. Several of the cells in the tumor microenvironment also produce RAGE ligands. Most of the cancer-promoting effects of RAGE ligands are the result of their interaction with RAGE. However, these ligands also often have separate intracellular roles, and some may interact with other extracellular targets, so it is not currently possible to assign all of their effects to RAGE activation. Despite these complications, the bulk of the evidence supports the premise that the ligand-RAGE axis is an important target for therapeutic intervention in cancer.

show abstract

Section: Breast Cancermentioning

confidence: 99%

RAGE and RAGE Ligands in Cancer

Logsdon

Fuentes

Huang

et al. 2007

CMM

187

170

View full text Add to dashboard Cite

show abstract

“…Human HMGB1 promoter is regulated by a silencer and an enhancer-containing intron (Lum and Lee, 2001). The sequence of HMGB1 promoter is TATA-less but contains three different CCAAT boxes (Nagatani et al, 2001).…”

Section: Hmgb1 Transcriptional Regulation (Figure 8)mentioning

confidence: 99%

HMGB1 in health and disease

Kang

Chen

Zhang

et al. 2014

Molecular Aspects of Medicine

822

828

View full text Add to dashboard Cite

Complex genetic and physiological variations as well as environmental factors that drive emergence of chromosomal instability, development of unscheduled cell death, skewed differentiation, and altered metabolism are central to the pathogenesis of human diseases and disorders. Understanding the molecular bases for these processes is important for the development of new diagnostic biomarkers, and for identifying new therapeutic targets. In 1973, a group of non-histone nuclear proteins with high electrophoretic mobility was discovered and termed High-Mobility Group (HMG) proteins. The HMG proteins include three superfamilies termed HMGB, HMGN, and HMGA. High-mobility group box 1 (HMGB1), the most abundant and well-studied HMG protein, senses and coordinates the cellular stress response and plays a critical role not only inside of the cell as a DNA chaperone, chromosome guardian, autophagy sustainer, and protector from apoptotic cell death, but also outside the cell as the prototypic damage associated molecular pattern molecule (DAMP). This DAMP, in conjunction with other factors, thus has cytokine, chemokine, and growth factor activity, orchestrating the inflammatory and immune response. All of these characteristics make HMGB1 a critical molecular target in multiple human diseases including infectious diseases, ischemia, immune disorders, neurodegenerative diseases, metabolic disorders, and cancer. Indeed, a number of emergent strategies have been used to inhibit HMGB1 expression, release, and activity in vitro and in vivo. These include antibodies, peptide inhbitiors, RNAi, anti-coagulants, endogenous hormones, various chemical compounds, HMGB1-receptor and signaling pathway inhibition, artificial DNAs, physical strategies including vagus nerve stimulation and other surgical approaches. Future work further investigating the details of HMGB1 localizationtion, structure, post-translational modification, and identifccation of additional partners will undoubtedly uncover additional secrets regarding HMGB1’s multiple functions.

show abstract

“…Immediately, upstream of the transcriptional start site is a silencer element that represses the transcriptional activity of the HMGB1 promoter by >80%. The transcriptional repression of the silencer element is offset by an enhancer element found in the first intron of the human HMGB1 gene and can increase the HMGB1 activity by 2-fold to 3-fold (19).…”

Section: Hmgb1gene/protein and Regulation Of Expressionmentioning

confidence: 99%

Masquerader: High Mobility Group Box-1 and Cancer

Ellerman

Brown

Vera

et al. 2007

Clinical Cancer Research

326

286

View full text Add to dashboard Cite

Since its identification a third of a century ago, the high-mobility group box-1 (HMGB1) protein has been linked to varied diverse cellular processes, including release from necrotic cells and secretion by activated macrophages engulfing apoptotic cells. Initially described as solely chromatin-associated, HMGB1 was additionally discovered in the cytoplasm of several types of cultured mammalian cells 6 years later. In addition to its intracellular role, HMGB1has been identified extracellularly as a putative leaderless cytokine and differentiation factor. In the years since its discovery, HMGB1has also been implicated in disease states, including Alzheimer's, sepsis, ischemia-reperfusion, arthritis, and cancer. In cancer, overexpression of HMGB1, particularly in conjunction with its receptor for advanced glycation end products, has been associated with the proliferation and metastasis of many tumor types, including breast, colon, melanoma, and others. This review focuses on current knowledge and speculation on the role of HMGB1in the development of cancer, metastasis, and potential targets for therapy.

show abstract

The human HMGB1 promoter is modulated by a silencer and an enhancer-containing intron

Cited by 23 publications

References 27 publications

RAGE and RAGE Ligands in Cancer

RAGE and RAGE Ligands in Cancer

HMGB1 in health and disease

Masquerader: High Mobility Group Box-1 and Cancer

Contact Info

Product

Resources

About