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

Autor: Borde C; Sorbonne Université, Institut National de la Santé et de la Recherche Médicale (INSERM) U938, Centre de Recherche Saint-Antoine, F-75012 Paris, France., Dillard C; Sorbonne Université, Institut National de la Santé et de la Recherche Médicale (INSERM) U938, Centre de Recherche Saint-Antoine, F-75012 Paris, France., L'Honoré A; Sorbonne Université, Centre National de la Recherche Scientifique (CNRS), INSERM, Institut de Biologie Paris-Seine, Biological Adaptation and Aging, B2A-IBPS, F-75005 Paris, France., Quignon F; Sorbonne Université, CNRS UMR 144, Institut Curie Centre de Recherche, F-75248 Paris, France., Hamon M; Centre National de la Recherche Scientifique (CNRS), Institut de Biologie Physico-Chimique, Plateforme de Protéomique, FR550, F-75005 Paris, France., Marchand CH; Centre National de la Recherche Scientifique (CNRS), Institut de Biologie Physico-Chimique, Plateforme de Protéomique, FR550, F-75005 Paris, France.; Sorbonne Université, Centre National de la Recherche Scientifique (CNRS), Institut de Biologie Paris-Seine, UMR7238, Laboratory of Computational and Quantitative Biology, F-75005 Paris, France.; Sorbonne Université, Centre National de la Recherche Scientifique (CNRS), Institut de Biologie Physico-Chimique, UMR8226, F-75005 Paris, France., Faccion RS; Sorbonne Université, Institut National de la Santé et de la Recherche Médicale (INSERM) U938, Centre de Recherche Saint-Antoine, F-75012 Paris, France.; Laboratório de Hemato-Oncologia Celular e Molecular, Programa de Hemato-Oncologia Molecular, Hospital do Câncer I, Centro de Pesquisas do Instituto Nacional de Câncer José Alencar Gomes da Silva (INCA), Praça da Cruz Vermelha 23/6° andar, Rio de Janeiro 20230-130, Brazil., Costa MGS; Fundação Oswaldo Cruz, Programa de Computação Científica, Vice-Presidência de Educação, Informação e Comunicação, Av. Brasil 4365, Manguinhos, Rio de Janeiro 21040-900, Brazil., Pramil E; Sorbonne Université, Institut National de la Santé et de la Recherche Médicale (INSERM) U938, Centre de Recherche Saint-Antoine, F-75012 Paris, France.; Alliance for Research in Cancerology-APREC, Tenon Hospital, F-75020 Paris, France., Larsen AK; Sorbonne Université, Institut National de la Santé et de la Recherche Médicale (INSERM) U938, Centre de Recherche Saint-Antoine, F-75012 Paris, France., Sabbah M; Sorbonne Université, Institut National de la Santé et de la Recherche Médicale (INSERM) U938, Centre de Recherche Saint-Antoine, F-75012 Paris, France., Lemaire SD; Sorbonne Université, Centre National de la Recherche Scientifique (CNRS), Institut de Biologie Paris-Seine, UMR7238, Laboratory of Computational and Quantitative Biology, F-75005 Paris, France.; Sorbonne Université, Centre National de la Recherche Scientifique (CNRS), Institut de Biologie Physico-Chimique, UMR8226, F-75005 Paris, France., Maréchal V; Sorbonne Université, Institut National de la Santé et de la Recherche Médicale (INSERM) U938, Centre de Recherche Saint-Antoine, F-75012 Paris, France., Escargueil AE; Sorbonne Université, Institut National de la Santé et de la Recherche Médicale (INSERM) U938, Centre de Recherche Saint-Antoine, F-75012 Paris, France.
Jazyk: angličtina
Zdroj: International journal of molecular sciences [Int J Mol Sci] 2022 Jul 17; Vol. 23 (14). Date of Electronic Publication: 2022 Jul 17.
DOI: 10.3390/ijms23147865
Abstrakt: 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.
Databáze: MEDLINE
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