HMGB1 for the treatment of tumors

The High Mobility Group B1 (HMGB1) protein belongs

to the High Mobility Group (HMG) family of nuclear proteins, which was named due to the unusual high mobility of its members in SDSpolyacrylamide gel electrophoresis (SDS-PAGE). These proteins are, second to histones, among the most abundant proteins associated with chromatin and they play an architectural role in the nucleus of the eukaryotic cell in that they bend, distort or otherwise modify the conformation of DNA, thereby also modifying the binding of transcription factors to DNA. HMG proteins have been implicated in the genesis of various disorders, like several kinds of benign tumors and autoimmune diseases. For the HMGB1 proteins, several structural motifs have been described: two DNA-binding domains (box A and box B), two nuclear localization sequences, and a C-terminal acidic domain. The HMGB1 proteins can be extensively posttranslationally modified by acetylation, methylation, ADPribosylation, phosphorylation or glycosylation. Acetylation of the nuclear localization sites is the signal that causes the HMGB1 protein to be actively secreted from activated cells of the immune system. Besides active secretion, HMGB1 is also released passively from necrotic cells.

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DKFZ (German Cancer Research Center, Deutsches Krebsforschungszentrum)
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Dr. Ruth Herzog