Evdokia A. Pasheva

High Mobility Group Box 1 (HMGB1) is a nuclear non-histone protein discovered to be released in the extracellular medium as a response to various stimuli and implicated in cancerogenesis. High HMGB1 levels are reported in a variety of tumor types, but there are few data relating HMGB1 to the histological grade or to a particular cell type and cellular localization. We studied the expression of HMGB1 protein in malignant human tumors of different differentiation level and in tumor metastasis. In all tumor tissues, the protein level is elevated. In moderately differentiated carcinomas, the localization of the protein is perinuclear, while in the low differentiated; there is a tendency for non-specific nuclear localization. HMGB1 protein and its receptor RAGE are identified as a ligand–receptor pair that plays an important role in regulating the invasiveness of tumor cells. RAGE is not produced in all of the tested tumor specimens. We found high level of expression in hepatocellular, colorectal, and breast cribriform carcinomas, but not in malignant testicular specimens. Probably, the RAGE synthesis is related to distinctive tumor types. In metastatic cells, RAGE exhibits higher level of expression losing its specific granular cytosolic pattern characteristic for the primary tumors.

High mobility group box (HMGB) proteins 1 and 2 are abundant non-histone nuclear proteins that regulate chromatin structure because of their structure-specific binding to DNA. Here, we have investigated how the post-synthetic acetylation of HMGB1 affects its interaction with negatively supercoiled DNA by employing monoacetylated at Lys2 protein, isolated from butyrate-treated cells. Our data reveal that this modification enhances three reaction parameters: binding affinity, supercoiling activity and capacity to protect the supercoiled DNA from relaxation by topoisomerase I. We show that monoacetylation at Lys2 mimics the effect of acidic tail removal but to a lesser extent thus demonstrating that in vivo acetylated HMGB1 is capable of modulating its interaction with negatively supercoiled DNA.