Analysis of Nuclear High Mobility Group Box 1 (HMGB1)-Binding Proteins in Colon Cancer Cells: Clustering with Proteins Involved in Secretion and Extranuclear Function

Lee, Hanna; Shin, Nara; Song, Minju; Kang, Un Beom; Yeom, Jeonghun; Lee, Cheolju; Ahn, Yeong Hee; Yoo, Jong Shin; Paik, Young Ki; Kim, Hoguen

doi:10.1021/pr100386r

Cited by 44 publications

(49 citation statements)

References 33 publications

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“…Furthermore, confocal microscopy images show that partial amounts of HMGB-1 were located in LAMP-1-positive lysosomes (Fig. 6D), as reported by a previous study (40). These data suggest that GNP-attenuated TLR9 signaling may be through interaction with HMGB-1 in lysosomes.…”

Section: Gnp Binds Hmgb-1 In the Lysosomessupporting

confidence: 87%

Size-Dependent Attenuation of TLR9 Signaling by Gold Nanoparticles in Macrophages

Tsai

et al. 2012

The Journal of Immunology

145

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Gold nanoparticles (GNPs), which are generally thought to be bio-inert and non-cytotoxic, have become one of the most ideal nanomaterials for medical applications. Once engulfed by phagocytes, the immunological effects of GNPs are still of concern and require detailed investigation. Therefore, this study explored the immunological significance of GNPs on TLR-mediated innate immunity in murine macrophages. GNP causes specific inhibition of TLR9 (CpG oligodeoxynucleotides; CpG-ODNs) signal in macrophages. The impaired CpG-ODN–induced TNF-α production is GNP concentration- and size-dependent in murine Raw264.7 cells: a GNP of 4 nm in size is more potent than a GNP of 11, 19, 35, or 45 nm in size. Consistent with cytokine inhibition, the CpG-ODN–induced phosphorylation of NF-κB and JNK as well as NF-κB activation are suppressed by GNPs. GNPs accumulate in lysosomes after phagocytosis and also increase TLR9-associated lysosomal cathepsin expression and activities, but this is irrelevant to TLR9 inhibition by GNPs in our studies. In addition, GNPs affected TLR9 translocation in response to CpG-ODNs and to phagosomes. Further exploring how GNPs inhibited TLR9 function, we found that GNPs could bind to high-mobility group box-1 (which is involved in the regulation of TLR9 signaling) inside the lysosomes. The current studies demonstrate that size-dependent inhibition of TLR9 function by GNP may be attributed to its binding to high-mobility group box-1.

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Section: Gnp Binds Hmgb-1 In the Lysosomessupporting

confidence: 87%

Size-Dependent Attenuation of TLR9 Signaling by Gold Nanoparticles in Macrophages

Tsai

et al. 2012

The Journal of Immunology

145

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“…These extracellular HMGB1 activities are not only mediated by receptors, but also by its Redox state and structure (Tang et al, 2012). Besides its nuclear and extracellular roles, cytoplasmic HMGB1 binds many proteins involved in autophagy (Tang et al, 2010c), cancer progression, and possibly the unconventional secretory pathway (Lee et al, 2010a). HMGB1 not only binds to DNA, but also interacts with many apparently unrelated proteins by recognizing short amino acid sequence motifs (Dintilhac and Bernues, 2002).…”

Section: Introduction and Historical Backgroundmentioning

confidence: 99%

HMGB1 in health and disease

Kang

Chen

Zhang

et al. 2014

Molecular Aspects of Medicine

798

828

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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.

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“…Isoform 1 of myosin-9 is a known binding protein that binds to a number of proteins related to cancer progression and the unconventional secretory pathway [79].…”

Section: +mentioning

confidence: 99%