HMGB1 in inflammation and cancer
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(2020) 13:116
EDITORIAL
Open Access
HMGB1 in inflammation and cancer Shumin Wang1,2,3 and Yi Zhang1,2,3*
Abstract High mobility group box 1 (HMGB1) is a non-histone chromatin-associated protein widely distributed in eukaryotic cells and is involved in DNA damage repair and genomic stability maintenance. In response to stimulus like bacteria or chemoradiotherapy, HMGB1 can translocate to extracellular context as a danger alarmin, activate the immune response, and participate in the regulation of inflammation and cancer progression. Keywords: HMGB1, RAGE, TLR, DAMP, Inflammation, Cancer High mobility group box 1 (HMGB1) is a highly conservative nucleoprotein and belongs to the group of nonhistone chromatin-associated protein. It was first extracted from calf-thymus chromatin in 1973 and named for its high mobility in gel electrophoresis [1]. Subsequent investigations found that HMGB1 could translocate from the nucleus to the cytoplasm after posttranslational modifications, including acetylation, phosphorylation, and methylation. HMGB1 can be expressed at the neuron membrane as well. In response to chemoradiotherapy or hypoxia, HMGB1 could be transferred to the extracellular context mainly through two ways: active secretion from immunocompetent cells or passive release from apoptotic or necrotic cells. Extracellular HMGB1 transmits danger signals to surrounding cells by interacting with its classical receptors, such as the receptor for advanced glycation end products (RAGE) and Toll-like receptors 2/4/9 (TLR-2/4/9) [2]. Indepth studies implicated that HMGB1 was a multifunctional protein involved in a variety of cellular biological properties, depending on its subcellular localization, post-transcriptional modification, and binding receptors (Fig. 1).
* Correspondence: [email protected] 1 Biotherapy Center & Cancer Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China 2 State Key Laboratory of Esophageal Cancer Prevention & Treatment, Zhengzhou University, Zhengzhou 450052, China Full list of author information is available at the end of the article
In the nucleus, HMGB1 plays a key role in the process of DNA replication, transcription, chromatin remodeling, and V(D)J recombination, thus regulating DNA damage repair and the maintenance of genome stability as a DNA chaperone. Cytoplasmic HMGB1 is involved in immune responses by increasing autophagy, inhibiting apoptosis, and regulating mitochondrial function [3]. At the membrane, HMGB1 promotes axonal sprouting and neurite growth, activates platelets, and induces cell migration. As a typical damage associated molecular pattern (DAMP), extracellular HMGB1 is involved in many immune responses by promoting immune cell maturation, activation and cytokine production [4]. Extracellular HMGB1 can also interact with chemokines such as CXCL11 to enhance immune responses [5]. As a multifunctional protein, HMGB1 exerts different biological effects under different stimuli. The deregulation of HMGB1 is associated with many diseases, especially
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