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. Author manuscript; available in PMC: 2015 May 19.
Published in final edited form as: Trends Biochem Sci. 2012 Nov 13;37(12):553–562. doi: 10.1016/j.tibs.2012.09.003

Figure 5. High mobility group box 1 (HMGB1) interactions in the cell.

Figure 5

The diagram summarizes and combines findings from studies of post-translational modifications and cysteine oxidation of HMGB1 that correlate with different functions and localization of HMGB1. The DNA-bound nuclear form of HMGB1 (yellow) is generally reduced, but phosphorylation (green ‘P’), methylation (cyan ‘Me’) and acetylation (blue ‘Ac’) can regulate DNA (in blue) binding activity. The cytoplasmic and extracellular forms of HMGB1 are generally more highly acetylated and oxidized than the nuclear form. Cytoplasmic HMGB1 can compete with Bcl-2 (grey) for binding to Beclin1 (blue), which promotes autophagy. Release of HMGB1 to the extracellular space, where it can act on receptors of the same as well as neighboring cells, results in different responses, depending on the receptor; receptor for advanced glyclation end products (RAGE, purple) promotes autophagy, whereas toll-like receptor 4 (TLR4, green) promotes cytokine release, and oxidized forms of HMBG1 can promote apoptosis. Reduced Cys 22, Cys 44 and Cys 106 are indicated by a black ‘C’. The oxidized Cys 22 and Cys 44 form a disulfide bond indicated by red ‘C-C’ and the oxidized C 106 sulfinic acid is represented by a black ‘C’ that has a red star outline. The specific placement of the marks is not meant to indicate where they are located in HMGB1.