G-quadruplexes sequester free heme in living cells
| Autor: | Nancy Maizels, Emilia Puig Lombardi, Alain Nicolas, Daniela Verga, Lucas T. Gray, Marie-Paule Teulade-Fichou, Arturo Londoño-Vallejo |
|---|---|
| Přispěvatelé: | Chimie, Modélisation et Imagerie pour la Biologie [Orsay], Université Paris-Sud - Paris 11 (UP11)-Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Dynamique de l'information génétique : bases fondamentales et cancer (DIG CANCER), Centre National de la Recherche Scientifique (CNRS)-Institut Curie [Paris]-Sorbonne Université (SU), Conception, synthèse et vectorisation de biomolécules. (CSVB), Université Paris Descartes - Paris 5 (UPD5)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut Curie [Paris], Université Paris-Sud - Paris 11 (UP11)-Institut Curie-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut Curie-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Institut Curie-Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5), Centre National de la Recherche Scientifique (CNRS) |
| Rok vydání: | 2019 |
| Předmět: |
Transcription
Genetic [SDV]Life Sciences [q-bio] Clinical Biochemistry Ligands Biochemistry 01 natural sciences chemistry.chemical_compound Transcription (biology) Drug Discovery Gene expression heterocyclic compounds Heme ComputingMilieux_MISCELLANEOUS chemistry.chemical_classification 0303 health sciences Oxidase test Fused-Ring Compounds biology [CHIM.ORGA]Chemical Sciences/Organic chemistry DNA Catalytic Cell biology Molecular Docking Simulation Molecular Medicine Cell Survival Iron 010402 general chemistry G-quadruplex Cofactor 03 medical and health sciences Cell Line Tumor [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry Molecular Biology/Genomics [q-bio.GN] Humans [SDV.BBM]Life Sciences [q-bio]/Biochemistry Molecular Biology Molecular Biology 030304 developmental biology Pharmacology [SDV.GEN]Life Sciences [q-bio]/Genetics Binding Sites 010405 organic chemistry Cell Cycle Checkpoints Porphyrin In vitro 0104 chemical sciences G-Quadruplexes Enzyme chemistry biology.protein [INFO.INFO-BI]Computer Science [cs]/Bioinformatics [q-bio.QM] Homeostasis |
| Zdroj: | Cell Chemical Biology Cell Chemical Biology, Cell Press, 2019, ⟨10.1016/j.chembiol.2019.10.003⟩ Cell Chemical Biology, Cell Press, 2019, 26 (12), pp.1681-1691.e5. ⟨10.1016/j.chembiol.2019.10.003⟩ |
| ISSN: | 2451-9456 |
| DOI: | 10.1101/652297 |
| Popis: | Heme is an essential cofactor for many enzymes, but free heme is toxic and its levels are tightly regulated. G-quadruplexes bind heme avidlyin vitro, raising the possibility that they may sequester hemein vivo. If so, then treatment that displaces heme from quadruplexes is predicted to induce expression of genes involved in iron and heme homeostasis. Here we show that PhenDC3, a G-quadruplex ligand structurally unrelated to heme, displaces quadruplex-bound hemein vitroand alters transcription in cultured human cells, up-regulating genes that support heme degradation and iron homeostasis, and most strikingly causing a 30-fold induction of heme oxidase 1, the key enzyme in heme degradation. We propose that G-quadruplexes sequester heme to protect cells from the pathophysiological consequences of free heme. This identifies a new function for G-quadruplexes and a new mechanism for protection of cells from heme. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|