BTBBCL6 dimers as building blocks for reversible drug-induced protein oligomerization
© 2022 The Author(s)..
Here, we characterize the BTB domain of the transcription factor BCL6 (BTBBCL6) as a small-molecule-controlled, reversible oligomerization switch, which oligomerizes upon BI-3802 treatment and de-oligomerizes upon addition of BI-3812. We show that the magnitude of oligomerization can be controlled in vitro by BI-3802 concentration and exposure time. In cellular models, exposure to BI-3802/BI-3812 can drive multiple cycles of foci formation consisting of BTBBCL6 fused to EGFP, which are not degraded due to the lack of a degron. We generated an epidermal growth factor receptor (EGFR)-BTBBCL6 fusion. Treatment with BI-3802, as an ON switch, induced EGFR-BTBBCL6 phosphorylation and activation of downstream effectors, which could in part be reversed by the addition of BI-3812, as an OFF switch. Finally, BI-3802-induced oligomerization of the EGFR-BTBBCL6 fusion enhanced proliferation of an EGF-dependent cell line in absence of EGF. These results demonstrate the successful application of small-molecule-induced, reversible oligomerization as a switch for synthetic biology.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2022 |
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| Erschienen: |
2022 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:2 |
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| Enthalten in: |
Cell reports methods - 2(2022), 4 vom: 25. Apr., Seite 100193 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Nitsch, Lena [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 02.10.2023 Date Revised 02.10.2023 published: Electronic-eCollection Citation Status MEDLINE |
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| doi: |
10.1016/j.crmeth.2022.100193 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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NLM34026277X |
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| 520 | |a © 2022 The Author(s). | ||
| 520 | |a Here, we characterize the BTB domain of the transcription factor BCL6 (BTBBCL6) as a small-molecule-controlled, reversible oligomerization switch, which oligomerizes upon BI-3802 treatment and de-oligomerizes upon addition of BI-3812. We show that the magnitude of oligomerization can be controlled in vitro by BI-3802 concentration and exposure time. In cellular models, exposure to BI-3802/BI-3812 can drive multiple cycles of foci formation consisting of BTBBCL6 fused to EGFP, which are not degraded due to the lack of a degron. We generated an epidermal growth factor receptor (EGFR)-BTBBCL6 fusion. Treatment with BI-3802, as an ON switch, induced EGFR-BTBBCL6 phosphorylation and activation of downstream effectors, which could in part be reversed by the addition of BI-3812, as an OFF switch. Finally, BI-3802-induced oligomerization of the EGFR-BTBBCL6 fusion enhanced proliferation of an EGF-dependent cell line in absence of EGF. These results demonstrate the successful application of small-molecule-induced, reversible oligomerization as a switch for synthetic biology | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, N.I.H., Extramural | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a BI-3802 | |
| 650 | 4 | |a BI-3812 | |
| 650 | 4 | |a BTB domain | |
| 650 | 4 | |a BTB switch | |
| 650 | 4 | |a polymerization switch | |
| 650 | 4 | |a protein polymerization | |
| 650 | 4 | |a reversibility | |
| 650 | 7 | |a Epidermal Growth Factor |2 NLM | |
| 650 | 7 | |a 62229-50-9 |2 NLM | |
| 650 | 7 | |a ErbB Receptors |2 NLM | |
| 650 | 7 | |a EC 2.7.10.1 |2 NLM | |
| 650 | 7 | |a BCL6 protein, human |2 NLM | |
| 650 | 7 | |a Proto-Oncogene Proteins c-bcl-6 |2 NLM | |
| 700 | 1 | |a Jensen, Patrizia |e verfasserin |4 aut | |
| 700 | 1 | |a Yoon, Hojong |e verfasserin |4 aut | |
| 700 | 1 | |a Koeppel, Jonas |e verfasserin |4 aut | |
| 700 | 1 | |a Burman, Shourya Sonkar Roy |e verfasserin |4 aut | |
| 700 | 1 | |a Fischer, Eric Sebastian |e verfasserin |4 aut | |
| 700 | 1 | |a Scholl, Claudia |e verfasserin |4 aut | |
| 700 | 1 | |a Fröhling, Stefan |e verfasserin |4 aut | |
| 700 | 1 | |a Słabicki, Mikołaj |e verfasserin |4 aut | |
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