Post‐Translational Modification of HMGB1 and Its Role in Immune Activation

Abstract

High-mobility group box 1 (HMGB1) is a non-histone nuclear protein with dual function. Inside the cell HMGB1 interacts with DNA to modify its structure and regulate transcription. Outside the cell HMGB1 serves as an alarmin to activate the innate immune system and promote tissue repair. The translocation of HMGB1 from inside to outside the cell is essential to the immunological activity of this protein and takes place primarily during cell activation and cell death. In these settings, HMGB1 may undergo post-translational modifications similar to those determining the epigenome. Whereas usual epigenetic modifications influence gene expression, with HMGB1 these modifications influence the location of the protein in the cell as well as its immunological activity.As described elsewhere in this volume, epigenetic modification of DNA and histones is a ubiquitous process regulating gene expression for differentiated cell function. These modifications represent a level of genetic information that extends beyond that encoded in the DNA itself. Although this information is distinct from the genome, it is nevertheless heritable [1,2]. The most prominent epigenetic modifications are CpG methylation of DNA and covalent modification of histones. Indeed, over 100 different post-translational protein modifications like methylation, phosphorylation, acetylation, ribosylation and ubiquitination characterize the epigenome [3,4].