Disease relevance of HMGB1

• HMG 1 protects 50% of highly negatively supercoiled DNA from E. coli topoisomerase I at a molar ratio of 100:1, and protects all supercoils at a molar ratio of 200:1, indicating saturation of the DNA at this concentration [1].
• High mobility group protein 1 preferentially conserves torsion in negatively supercoiled DNA [1].

High impact information on HMGB1

• Autoradiography of thin sections showed that 125I-labeled HMG1 localized within nuclei, and further established that it remained associated with metaphase chromosomes at mitosis [2].
• Similar results were obtained with bovine fibroblasts, indicating that a dynamic equilibrium exists between HMG1 and chromatin within living cells [2].
• Here, we show that extracellular HMGB1 and its receptor for advanced glycation end products (RAGE) induce both migration and proliferation of vessel-associated stem cells (mesoangioblasts), and thus may play a role in muscle tissue regeneration [3].
• Peptides corresponding to the N-terminal, central and central plus C-terminal domains of high mobility group protein HMG-1 from calf thymus have been isolated after digestion in solution with protease V8 under structuring conditions (0.35 M NaCl, pH 7.1) [4].
• Accordingly, RAGE blockade by neutralizing Abs inhibits HMGB1-induced neovascularization in vivo and endothelial cell proliferation and membrane ruffling in vitro [5].

Biological context of HMGB1

• Determination of the DNA sequences in these clones indicates that they represent the 3' half of the HMG-1 message and contain an unusually long putative 3' untranslated region of 480 nucleotides [6].
• The chromatin high mobility group protein 1 (HMGB1) is a very abundant and conserved protein that is structured into two HMG box domains plus a highly acidic C-terminal domain [7].
• When antibodies to bovine HMG-1 were microinjected into nuclei of living oocytes of Pleurodeles the lateral loops of the lampbrush chromosomes gradually retracted and the whole chromosomes condensed [8].
• Phosphorylation of high mobility group protein 14 by casein kinase II [9].
• Studies of acetylation and deacetylation in high mobility group proteins. Identification of the sites of acetylation in HMG-1 [10].

Anatomical context of HMGB1

• In keeping with its in vitro properties, HMGB1 stimulates neovascularization when applied in vivo on the top of the chicken embryo chorioallantoic membrane whose blood vessels express the HMGB1 receptor for advanced glycation end products (RAGE) [5].
• We isolated hybridomas secreting monoclonal antibodies against HMG-1 [11].
• Histone and high mobility group protein phosphorylation in the thyroid: regulation by cyclic nucleotides [12].
• Regulation of type-II collagen gene expression during human chondrocyte de-differentiation and recovery of chondrocyte-specific phenotype in culture involves Sry-type high-mobility-group box (SOX) transcription factors [13].
• Differential phosphorylation of high mobility group protein hmg 14 from calf thymus and avian erythrocytes by a cyclic gmp-dependent protein kinase [14].

Associations of HMGB1 with chemical compounds

• High mobility group proteins 1 and 2 bind preferentially to brominated poly(dG-dC).poly(dG-dC) in the Z-DNA conformation but not to other types of Z-DNA [15].
• Affinity purification of newly phosphorylated protein molecules. Thiophosphorylation and recovery of histones H1, H2B, and H3 and the high mobility group protein HMG-1 using adenosine 5'-O-(3-thiotriphosphate) and cyclic AMP-dependent protein kinase [16].
• The high mobility group protein 1 enhances binding of the estrogen receptor DNA binding domain to the estrogen response element [17].
• The isolation and partial sequence of peptides produced by cyanogen bromide cleavage of calf thymus non-histone chromosomal high-mobility-group protein 2. Sequence homology with non-histone chromosomal high-mobility-group protein 1 [18].
• The specific interactions of HMG 1 and 2 with negatively supercoiled DNA are modulated by their acidic C-terminal domains and involve cysteine residues in their HMG 1/2 boxes [19].

Other interactions of HMGB1

• Quantitative microcomplement fixation assays revealed that the indices of dissimilarity between HMG-1 and HMG-2, HMG-3, HMG-8, HMG-14, and HMG-17 were 2.0, 1.0, 3.8, 10.0, and 6.1, respectively [20].
• These correspond to 6%, 0%, 12%, 20%, and 16% sequence difference between HMG-1 and the other five HMG proteins, although the immunological distance between HMG-1 and HMG-14 may be too large to allow a good correlation between the sequence and the immunological reaction [20].
• Assignment of syndecan 2 (SDC2)gene to cattle chromosome band 14q22 and thymus high mobility group box protein TOX (TOX)(2) gene to cattle chromosome band 14q17-->q18 by in situ hybridization [21].

Analytical, diagnostic and therapeutic context of HMGB1

• Based on the analysis of FTIR and UV-CD spectra, the interaction of DNA with nonhistone chromatin protein HMGB1 and linker histone H1 was studied [22].
• The ternary complex, DNA X HMG1 X 1, seemed to represent a specific structure, since its formation depeNded on the reduced sulfhydryl state of HMG1; the disulfide form of HMG1, which was shown by circular dichroism to contain more random coil than did the reduced form, had no effect on the circular dichroic spectrum of the DNA X H1 complex [23].
• (iii) Electron microscopy shows that HMG3 at a low protein:DNA input ratio (1:1 w/w; r = 1), and HMG1 at a 6-fold higher ratio, cause looping of relaxed circular DNA at 150 mM ionic strength [24].
• Oxidized forms of non-histone chromosomal proteins high mobility group 1 (HMG1) and HMG2 were detected by high-pressure liquid chromatography of preparations stored at 4 degrees C for 1 day [25].
• Western blotting and transcription reconstituted with purified factors show a copurification of HMG-1 and -2 with factor II B, described earlier by Reinberg and Roeder [(1987) J. Biol. Chem. 262, 3310-3321] [26].

References