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The C-Terminal Acidic Tail Modulates the Anticancer Properties of HMGB1

Abstract : Energy metabolism reprogramming was recently listed as a hallmark of cancer. In this process, the switch from pyruvate kinase isoenzyme type M1 to pyruvate kinase isoenzyme type M2 (PKM2) is believed to play a crucial role. Interestingly, the activity of the active form of PKM2 can efficiently be inhibited by the high-mobility group box 1 (HMGB1) protein, leading to a rapid blockage of glucose-dependent aerobic respiration and cancer cell death. HMGB1 is a member of the HMG protein family. It contains two DNA-binding HMG-box domains and an acidic C-terminal tail capable of positively or negatively modulating its biological properties. In this work, we report that the deletion of the C-terminal tail of HMGB1 increases its activity towards a large panel of cancer cells without affecting the viability of normal immortalized fibroblasts. Moreover, in silico analysis suggests that the truncated form of HMGB1 retains the capacity of the full-length protein to interact with PKM2. However, based on the capacity of the cells to circumvent oxidative phosphorylation inhibition, we were able to identify either a cytotoxic or cytostatic effect of the proteins. Together, our study provides new insights in the characterization of the anticancer activity of HMGB1.
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https://hal-cnrs.archives-ouvertes.fr/hal-03867377
Contributor : Michèle Sabbah Connect in order to contact the contributor
Submitted on : Wednesday, November 23, 2022 - 12:24:47 PM
Last modification on : Friday, November 25, 2022 - 4:01:44 AM

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Chloé Borde, Clémentine Dillard, Aurore L’honoré, Frédérique Quignon, Marion Hamon, et al.. The C-Terminal Acidic Tail Modulates the Anticancer Properties of HMGB1. International Journal of Molecular Sciences, 2022, 23 (14), pp.7865. ⟨10.3390/ijms23147865⟩. ⟨hal-03867377⟩

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