Super-enhancer trapping by the nuclear pore via intrinsically disordered regions of proteins in squamous cell carcinoma cells
Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved..
Master transcription factors such as TP63 establish super-enhancers (SEs) to drive core transcriptional networks in cancer cells, yet the spatiotemporal regulation of SEs within the nucleus remains unknown. The nuclear pore complex (NPC) may tether SEs to the nuclear pore where RNA export rates are maximal. Here, we report that NUP153, a component of the NPC, anchors SEs to the NPC and enhances TP63 expression by maximizing mRNA export. This anchoring is mediated through protein-protein interaction between the intrinsically disordered regions (IDRs) of NUP153 and the coactivator BRD4. Silencing of NUP153 excludes SEs from the nuclear periphery, decreases TP63 expression, impairs cellular growth, and induces epidermal differentiation of squamous cell carcinoma. Overall, this work reveals the critical roles of NUP153 IDRs in the regulation of SE localization, thus providing insights into a new layer of gene regulation at the epigenomic and spatial level.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:31 |
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| Enthalten in: |
Cell chemical biology - 31(2024), 4 vom: 18. Apr., Seite 792-804.e7 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Hazawa, Masaharu [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 22.04.2024 Date Revised 22.04.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.chembiol.2023.10.005 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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NLM364166657 |
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| 100 | 1 | |a Hazawa, Masaharu |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Super-enhancer trapping by the nuclear pore via intrinsically disordered regions of proteins in squamous cell carcinoma cells |
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| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved. | ||
| 520 | |a Master transcription factors such as TP63 establish super-enhancers (SEs) to drive core transcriptional networks in cancer cells, yet the spatiotemporal regulation of SEs within the nucleus remains unknown. The nuclear pore complex (NPC) may tether SEs to the nuclear pore where RNA export rates are maximal. Here, we report that NUP153, a component of the NPC, anchors SEs to the NPC and enhances TP63 expression by maximizing mRNA export. This anchoring is mediated through protein-protein interaction between the intrinsically disordered regions (IDRs) of NUP153 and the coactivator BRD4. Silencing of NUP153 excludes SEs from the nuclear periphery, decreases TP63 expression, impairs cellular growth, and induces epidermal differentiation of squamous cell carcinoma. Overall, this work reveals the critical roles of NUP153 IDRs in the regulation of SE localization, thus providing insights into a new layer of gene regulation at the epigenomic and spatial level | ||
| 650 | 4 | |a Journal Article | |
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| 650 | 4 | |a intrinsically disordered regions | |
| 650 | 4 | |a mRNA export | |
| 650 | 4 | |a nuclear pore complex | |
| 650 | 4 | |a p63 | |
| 650 | 4 | |a phase separation | |
| 650 | 4 | |a squamous cell carcinoma | |
| 650 | 4 | |a super-enhancer | |
| 650 | 7 | |a Transcription Factors |2 NLM | |
| 650 | 7 | |a Nuclear Proteins |2 NLM | |
| 650 | 7 | |a Nuclear Pore Complex Proteins |2 NLM | |
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| 650 | 7 | |a BRD4 protein, human |2 NLM | |
| 650 | 7 | |a Bromodomain Containing Proteins |2 NLM | |
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| 700 | 1 | |a Ikliptikawati, Dini Kurnia |e verfasserin |4 aut | |
| 700 | 1 | |a Iwashima, Yuki |e verfasserin |4 aut | |
| 700 | 1 | |a Lin, De-Chen |e verfasserin |4 aut | |
| 700 | 1 | |a Jiang, Yuan |e verfasserin |4 aut | |
| 700 | 1 | |a Qiu, Yujia |e verfasserin |4 aut | |
| 700 | 1 | |a Makiyama, Kei |e verfasserin |4 aut | |
| 700 | 1 | |a Matsumoto, Koki |e verfasserin |4 aut | |
| 700 | 1 | |a Kobayashi, Akiko |e verfasserin |4 aut | |
| 700 | 1 | |a Nishide, Goro |e verfasserin |4 aut | |
| 700 | 1 | |a Keesiang, Lim |e verfasserin |4 aut | |
| 700 | 1 | |a Yoshino, Hironori |e verfasserin |4 aut | |
| 700 | 1 | |a Minamoto, Toshinari |e verfasserin |4 aut | |
| 700 | 1 | |a Suzuki, Takeshi |e verfasserin |4 aut | |
| 700 | 1 | |a Kobayashi, Isao |e verfasserin |4 aut | |
| 700 | 1 | |a Meguro-Horike, Makiko |e verfasserin |4 aut | |
| 700 | 1 | |a Jiang, Yan-Yi |e verfasserin |4 aut | |
| 700 | 1 | |a Nishiuchi, Takumi |e verfasserin |4 aut | |
| 700 | 1 | |a Konno, Hiroki |e verfasserin |4 aut | |
| 700 | 1 | |a Koeffler, H Phillip |e verfasserin |4 aut | |
| 700 | 1 | |a Hosomichi, Kazuyoshi |e verfasserin |4 aut | |
| 700 | 1 | |a Tajima, Atsushi |e verfasserin |4 aut | |
| 700 | 1 | |a Horike, Shin-Ichi |e verfasserin |4 aut | |
| 700 | 1 | |a Wong, Richard W |e verfasserin |4 aut | |
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