Academic Journal
Distinct nuclear localization signals confer differential microtubule dependence among ZFTA fusion oncoproteins.
| Τίτλος: | Distinct nuclear localization signals confer differential microtubule dependence among ZFTA fusion oncoproteins. |
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| Συγγραφείς: | Ishii M; Research Institute of Pharmaceutical Sciences, Faculty of Pharmacy, Musashino University, Nishitokyo, Tokyo, Japan. Electronic address: m_ishii@musashino-u.ac.jp., Suto N; Drug Discovery Initiative (DDI), Graduate School of Pharmaceutical Sciences, The University of Tokyo, Bunkyo, Tokyo, Japan., Kojima R; Research Institute of Pharmaceutical Sciences, Faculty of Pharmacy, Musashino University, Nishitokyo, Tokyo, Japan., Katakawa K; Research Institute of Pharmaceutical Sciences, Faculty of Pharmacy, Musashino University, Nishitokyo, Tokyo, Japan; Department of Clinical Pharmacy, Faculty of Pharmaceutical Sciences, Shonan University of Medical Sciences, Yokohama, Kanagawa, Japan., Makino K; Research Institute of Pharmaceutical Sciences, Faculty of Pharmacy, Musashino University, Nishitokyo, Tokyo, Japan., Toma-Fukai S; Graduate School of Science and Technology, Nara Institute of Science and Technology, Ikoma, Nara, Japan., Tsusaka T; Research Institute of Pharmaceutical Sciences, Faculty of Pharmacy, Musashino University, Nishitokyo, Tokyo, Japan., Sueki S; Research Institute of Pharmaceutical Sciences, Faculty of Pharmacy, Musashino University, Nishitokyo, Tokyo, Japan., Anada M; Research Institute of Pharmaceutical Sciences, Faculty of Pharmacy, Musashino University, Nishitokyo, Tokyo, Japan., Kojima H; Drug Discovery Initiative (DDI), Graduate School of Pharmaceutical Sciences, The University of Tokyo, Bunkyo, Tokyo, Japan., Ohata S; Research Institute of Pharmaceutical Sciences, Faculty of Pharmacy, Musashino University, Nishitokyo, Tokyo, Japan. Electronic address: shiohata@musashino-u.ac.jp. |
| Πηγή: | The Journal of biological chemistry [J Biol Chem] 2026 Sep; Vol. 302 (9), pp. 113320. Date of Electronic Publication: 2026 Jul 13. |
| Τύπος έκδοσης: | Journal Article |
| Γλώσσα: | English |
| Στοιχεία περιοδικού: | Publisher: Elsevier Inc. on behalf of American Society for Biochemistry and Molecular Biology Country of Publication: United States NLM ID: 2985121R Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1083-351X (Electronic) Linking ISSN: 00219258 NLM ISO Abbreviation: J Biol Chem Subsets: MEDLINE |
| Imprint Name(s): | Publication: 2021- : [New York, NY] : Elsevier Inc. on behalf of American Society for Biochemistry and Molecular Biology Original Publication: Baltimore, MD : American Society for Biochemistry and Molecular Biology |
| Ιατρικοί όροι (MeSH): | Microtubules*/metabolism , Oncogene Proteins, Fusion*/metabolism , Oncogene Proteins, Fusion*/genetics , Oncogene Proteins, Fusion*/chemistry , Nuclear Localization Signals*/metabolism, Colchicine/pharmacology ; Colchicine/chemistry ; Tubulin Modulators/pharmacology ; Humans ; Animals |
| Περίληψη: | Ependymomas are glial tumors that exhibit high resistance to chemotherapy. ZFTA-fusion-positive supratentorial ependymoma (ST-EPN-ZFTA) represents a subclass with a poor prognosis. ST-EPN-ZFTA expresses fusion proteins, which consist of zinc finger translocation-associated (ZFTA) combined with a transcriptional regulator, predominantly RELA. Unlike wild-type RELA, which translocates to the nucleus in a stimulus-dependent manner, ZFTA-RELA constitutively localizes to the nucleus and induces oncogenic gene expression. To identify inhibitors of this aberrant gene expression, 9600 structurally diverse compounds were screened using a ZFTA-RELA-responsive luciferase reporter system. The screen identified a colchicine derivative, and subsequent evaluation revealed colchicine, a microtubule polymerization inhibitor, as the most potent inhibitor (IC (Copyright © 2026 The Authors. Published by Elsevier Inc. All rights reserved.) |
| Competing Interests: | Conflict of interest The authors declare that they have no conflicts of interest with the contents of this article. |
| Contributed Indexing: | Keywords: ZFTA; colchicine; dynein; ependymoma; microtubule; nuclear localization |
| Substance Nomenclature: | 0 (Oncogene Proteins, Fusion) 0 (Nuclear Localization Signals) SML2Y3J35T (Colchicine) 0 (Tubulin Modulators) |
| Entry Date(s): | Date Created: 20260713 Date Completed: 20260922 Latest Revision: 20260922 |
| Update Code: | 20260923 |
| PubMed Central ID: | PMC13474238 |
| DOI: | 10.1016/j.jbc.2026.113320 |
| PMID: | 42442495 |
| Βάση Δεδομένων: | MEDLINE |
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