HMGB1 interacts differentially with members of the Rel family of transcription factors

Agresti, A; Lupo, Rossella; Bianchi, Marco E.; Müller, Susanne

doi:10.1016/s0006-291x(03)00184-0

Cited by 87 publications

(61 citation statements)

References 28 publications

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“…This selective effect on the steroid class of nuclear receptors is dependent on the CTE and correlates with a direct protein interaction between HMGB-1/-2 and the CTE that does not occur with class II receptors (14,20). HMGB-1/-2 also interacts with select groups of apparently unrelated sequence-specific transcription factors including p53 (22), p73 (23), Hox proteins (24), Oct proteins (25), Rel family members (26), and EBV transcription factors Rta and Zebra (27,28), to enhance their binding to cognate DNA sequences and transcription activity.…”

mentioning

confidence: 98%

The Role of the C-terminal Extension (CTE) of the Estrogen Receptor α and β DNA Binding Domain in DNA Binding and Interaction with HMGB

Melvin

Harrell

Adelman

et al. 2004

Journal of Biological Chemistry

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HMGB-1/-2 are coregulatory proteins that facilitate the DNA binding and transcriptional activity of steroid receptor members of the nuclear receptor family of transcription factors. We investigated the influence and mechanism of action of HMGB-1/-2 (formerly known as HMG-1/-2) on estrogen receptor ␣ (ER␣) and ER␤. Both ER subtypes were responsive to HMGB-1/-2 with respect to enhancement of receptor DNA binding affinity and transcriptional activity in cells. Responsiveness to HMGB-1/-2 was dependent on the C-terminal extension (CTE) region of the ER DNA binding domain (DBD) and correlated with a direct protein interaction between HMGB-1/-2 and the CTE. Thus the previously reported higher DNA binding affinity and transcription activity of ER␣ as compared with ER␤ is not due to a lack of ER␤ interaction with HMGB-1/-2. Using chimeric receptor DBDs, the higher intrinsic DNA binding affinity of ER␣ than ER␤ was shown to be due to a unique property of the ER␣ CTE, independent of HMGB-1/-2. The CTE of both ER subtypes was also shown to be required for interaction with ERE half-sites. These studies reveal the importance of the CTE and HMGB-1/-2 for ER␣ and ER␤ interaction with their cognate target DNAs.Nuclear hormone receptors comprise a superfamily of liganddependent transcription factors that regulate gene expression through interaction with specific hormone response elements (HREs) 1 in target genes. The superfamily can be subdivided into: 1) classical steroid hormone receptors that typically interact with palindromic hexameric HREs as homodimers, 2) nonsteroidal or class II nuclear receptors for ligands such as thyroid hormone, retinoic acid, vitamin D, and fatty acids, that function primarily as heterodimers with RXR (retinoid X receptor) bound to direct repeat HREs, and 3) orphan receptors without known ligands that interact with HREs in various dimer and monomer configurations. The nuclear receptors are related through a common domain structure including conserved C-terminal ligand binding (LBD) and centrally located DNA binding domains (DBD), and a variable N-terminal domain that is required in many nuclear receptors for maximal transcription activity (Refs. 1 and 2, reviews). The DBD consists of a highly conserved core with two asymmetric zinc fingers and an ϳ30 amino acid segment, termed the C-terminal extension (CTE) (Fig. 1A). Within the core DBD, ␣-helix 1 extends between the two zinc fingers and makes base specific contacts in the major groove of the HRE DNA. The second ␣-helix (helix 2) does not contact DNA but is important for the overall folding of the core DBD (3-5). The CTE is not conserved and adopts different structural motifs dependent on the class of nuclear receptor (6, 7). Nonetheless, the CTE of different receptors does appear to share a functional role to stabilize the receptor-DNA complex by extending the protein-DNA interface beyond that of base-specific contacts made by the core DBD. The CTE of class II receptors (TR and VDR) forms an ␣-helix (helix 3) that projects across the minor groove...

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confidence: 98%

The Role of the C-terminal Extension (CTE) of the Estrogen Receptor α and β DNA Binding Domain in DNA Binding and Interaction with HMGB

Melvin

Harrell

Adelman

et al. 2004

Journal of Biological Chemistry

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“…HMGB1 was initially described as a nuclear nonhistone DNA-binding protein that functions as a structural cofactor critical for proper transcriptional regulation (6). It also facilitates numerous nuclear events, including replication, recombination, and DNA transposition (7).…”

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confidence: 99%

Bacterial Endotoxin Induces the Release of High Mobility Group Box 1 via the IFN-β Signaling Pathway

Kim

Lee

et al. 2009

The Journal of Immunology

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Sepsis is a devastating condition characterized by a systemic inflammatory response. Recently, high mobility group box 1 (HMGB1) was identified as a necessary and sufficient mediator of the lethal systemic inflammation caused by sepsis. However, despite its clinical importance, the mechanism of HMGB1 release has remained to be elusive. In this study, we demonstrate that the IFN-β-mediated JAK/STAT pathway is essential for LPS or Escherichia coli-induced HMGB1 release, which is dependent on Toll/IL-1R domain-containing adapter-inducing IFN-β adaptor. Additionally, we show that NO acts as a downstream molecule of the IFN-β signaling. Furthermore, the JAK inhibitor treatment as well as the STAT-1 or IFN-β receptor deficiency reduced HMGB1 release in a murine model of endotoxemia. Our results suggest that HMGB1 release in sepsis is dependent on the IFN-β signaling axis; thus, therapeutic agents that selectively inhibit IFN-β signaling could be beneficial in the treatment of sepsis.

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“…Inside the cell, HMGB1 binds to DNA and promotes transcription as well as other functions (1,2). Outside the cell, HMGB1 can serve as a cytokine to promote inflammation and induce an array of proinflammatory responses including the expression of TNF-␣, IL-1, and NO, as well as induce the maturation of dendritic cells (3).…”

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confidence: 99%

The Relationship between Apoptosis and High-Mobility Group Protein 1 Release from Murine Macrophages Stimulated with Lipopolysaccharide or Polyinosinic-Polycytidylic Acid

Jiang

Bell

Pisetsky

2007

The Journal of Immunology

123

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High-mobility group protein 1 (HMGB1) is a nonhistone nuclear protein whose function depends on cellular location. Inside the cell, HMGB1 modulates a variety of important cellular processes, including transcription, whereas outside the cell, HMGB1 acts as a cytokine that can promote inflammation and mediate sepsis and arthritis in animal models. In in vitro studies, proinflammatory molecules such as LPS, lipoteichoic acid, polyinosinic-polycytidylic acid (poly(I:C)), TNF-α, and type I and II IFNs can induce HMGB1 release from macrophages. Although these agents can activate cells, they can also induce apoptosis under certain circumstances. Therefore, because of evidence that apoptotic as well as necrotic cells can contribute to HMGB1-mediated events in sepsis, we have investigated the relationship between apoptosis and HMGB1 release in macrophages and other cells. In these experiments, using RAW 264.7 cells as a model, LPS and poly(I:C) caused HMGB1 release into the medium whereas CpG ODN failed to induce this response. With both LPS and poly(I:C), the extent of HMGB1 release correlated with the occurrence of apoptosis as measured by caspase 3 activation, lactate dehydrogenase release, and TUNEL staining. Similar results were obtained with primary murine macrophages as well as human Jurkat T cells. For Jurkat cells, poly(I:C) and NO donors induced apoptosis as well as HMGB1 release. Together, these results indicate that HMGB1 release from macrophages is correlated with the occurrence of apoptosis and suggest that these processes reflect common mechanisms and can occur concomitantly.

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HMGB1 interacts differentially with members of the Rel family of transcription factors

Cited by 87 publications

References 28 publications

The Role of the C-terminal Extension (CTE) of the Estrogen Receptor α and β DNA Binding Domain in DNA Binding and Interaction with HMGB

The Role of the C-terminal Extension (CTE) of the Estrogen Receptor α and β DNA Binding Domain in DNA Binding and Interaction with HMGB

Bacterial Endotoxin Induces the Release of High Mobility Group Box 1 via the IFN-β Signaling Pathway

The Relationship between Apoptosis and High-Mobility Group Protein 1 Release from Murine Macrophages Stimulated with Lipopolysaccharide or Polyinosinic-Polycytidylic Acid

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