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- Title
The C-Terminal Acidic Tail Modulates the Anticancer Properties of HMGB1.
- Authors
Borde, Chloé; Dillard, Clémentine; L'Honoré, Aurore; Quignon, Frédérique; Hamon, Marion; Marchand, Christophe H.; Faccion, Roberta Soares; Costa, Maurício G. S.; Pramil, Elodie; Larsen, Annette K.; Sabbah, Michèle; Lemaire, Stéphane D.; Maréchal, Vincent; Escargueil, Alexandre E.
- 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.
- Subjects
HIGH mobility group proteins; CELL respiration; OXIDATIVE phosphorylation; CANCER cells; ENERGY metabolism; PYRUVATE kinase
- Publication
International Journal of Molecular Sciences, 2022, Vol 23, Issue 14, p7865
- ISSN
1661-6596
- Publication type
Article
- DOI
10.3390/ijms23147865