دورية أكاديمية
A progesterone derivative linked to a stable phospholipid activates breast cancer cell response without leaving the cell membrane.
| العنوان: | A progesterone derivative linked to a stable phospholipid activates breast cancer cell response without leaving the cell membrane. |
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| المؤلفون: | Font-Mateu J; Center for Genomic Regulation (CRG), Barcelona Institute for Science and Technology (BIST), Barcelona, Spain., Sanllehí P; Center for Genomic Regulation (CRG), Barcelona Institute for Science and Technology (BIST), Barcelona, Spain.; Department of Biological Chemistry, Institute for Advanced Chemistry of Catalonia, IQAC-CSIC, Jordi Girona 18-26, 08034, Barcelona, Spain., Sot J; Instituto Biofisika (UPV/EHU, CSIC), Barrio Sarriena s/n, 48940, Leioa, Spain., Abad B; SGIKER, Universidad del País Vasco, Barrio Sarriena s/n, 48940, Leioa, Spain., Mateos N; The Barcelona Institute for Science and Technology (BIST), ICFO-Institut de Ciencies Fotòniques, 08860, Barcelona, Spain., Torreno-Pina JA; Center for Genomic Regulation (CRG), Barcelona Institute for Science and Technology (BIST), Barcelona, Spain.; The Barcelona Institute for Science and Technology (BIST), ICFO-Institut de Ciencies Fotòniques, 08860, Barcelona, Spain., Ferrari R; Department of Chemistry, Life Sciences and Environmental Sustainability, University of Parma, Parma, Italy., Wright RHG; Center for Genomic Regulation (CRG), Barcelona Institute for Science and Technology (BIST), Barcelona, Spain.; Faculty of Medicine and Health Sciences, Universitat Internacional de Catalunya, 08195, Sant Cugat del Vallès, Barcelona, Spain., Garcia-Parajo MF; The Barcelona Institute for Science and Technology (BIST), ICFO-Institut de Ciencies Fotòniques, 08860, Barcelona, Spain.; ICREA, Pg. Lluis Companys 23, 08010, Barcelona, Spain., Joglar J; Department of Biological Chemistry, Institute for Advanced Chemistry of Catalonia, IQAC-CSIC, Jordi Girona 18-26, 08034, Barcelona, Spain., Goñi FM; Instituto Biofisika (UPV/EHU, CSIC), Barrio Sarriena s/n, 48940, Leioa, Spain. felix.goni@ehu.es.; Departamento de Bioquímica y Biología Molecular, Universidad del País Vasco, Barrio Sarriena s/n, 48940, Leioa, Spain. felix.goni@ehu.es., Beato M; Center for Genomic Regulation (CRG), Barcelona Institute for Science and Technology (BIST), Barcelona, Spain. miguel.beato@crg.eu.; Universitat Pompeu Fabra (UPF), Barcelona, Spain. miguel.beato@crg.eu. |
| المصدر: | Cellular and molecular life sciences : CMLS [Cell Mol Life Sci] 2024 Feb 22; Vol. 81 (1), pp. 98. Date of Electronic Publication: 2024 Feb 22. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Springer Country of Publication: Switzerland NLM ID: 9705402 Publication Model: Electronic Cited Medium: Internet ISSN: 1420-9071 (Electronic) Linking ISSN: 1420682X NLM ISO Abbreviation: Cell Mol Life Sci Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: Basel : Springer Original Publication: Basel ; Boston : Birkhauser, c1997- |
| مواضيع طبية MeSH: | Progesterone*/pharmacology , Neoplasms*, Receptors, Progesterone/genetics ; Estrogen Receptor alpha ; Progestins/pharmacology ; Ligands ; Cell Membrane |
| مستخلص: | In hormone-responsive breast cancer cells, progesterone (P4) has been shown to act via its nuclear receptor (nPR), a ligand-activated transcription factor. A small fraction of progesterone receptor is palmitoylated and anchored to the cell membrane (mbPR) forming a complex with estrogen receptor alpha (ERα). Upon hormone exposure, either directly or via interaction with ERα, mbPR activates the SRC/RAS/ERK kinase pathway leading to phosphorylation of nPR by ERK. Kinase activation is essential for P4 gene regulation, as the ERK and MSK1 kinases are recruited by the nPR to its genomic binding sites and trigger chromatin remodeling. An interesting open question is whether activation of mbPR can result in gene regulation in the absence of ligand binding to intracellular progesterone receptor (iPR). This matter has been investigated in the past using P4 attached to serum albumin, but the attachment is leaky and albumin can be endocytosed and degraded, liberating P4. Here, we propose a more stringent approach to address this issue by ensuring attachment of P4 to the cell membrane via covalent binding to a stable phospholipid. This strategy identifies the actions of P4 independent from hormone binding to iPR. We found that a membrane-attached progestin can activate mbPR, the ERK signaling pathway leading to iPR phosphorylation, initial gene regulation and entry into the cell cycle, in the absence of detectable intracellular progestin. (© 2024. The Author(s).) |
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| معلومات مُعتمدة: | 609989 International ERC_ European Research Council; Impacct 825176 International ERC_ European Research Council |
| فهرسة مساهمة: | Keywords: Breast cancer cells; Cell membrane phospholipids; Nuclear hormone receptors; Progesterone receptor; Progesterone signaling |
| المشرفين على المادة: | 4G7DS2Q64Y (Progesterone) 0 (Receptors, Progesterone) 0 (Estrogen Receptor alpha) 0 (Progestins) 0 (Ligands) |
| تواريخ الأحداث: | Date Created: 20240222 Date Completed: 20240223 Latest Revision: 20240225 |
| رمز التحديث: | 20240225 |
| مُعرف محوري في PubMed: | PMC10884080 |
| DOI: | 10.1007/s00018-024-05116-3 |
| PMID: | 38386110 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 1420-9071 |
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| DOI: | 10.1007/s00018-024-05116-3 |