Taspase1 Facilitates Topoisomerase IIβ-Mediated DNA Double-Strand Breaks Driving Estrogen-Induced Transcription
The human protease Taspase1 plays a pivotal role in developmental processes and cancerous diseases by processing critical regulators, such as the leukemia proto-oncoprotein MLL. Despite almost two decades of intense research, Taspase1’s biology is, however, still poorly understood, and so far its ce...
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| Format: | Article |
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MDPI AG
2023-01-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/12/3/363 |
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| author | Lisa Oelschläger Paul Stahl Farnusch Kaschani Roland H. Stauber Shirley K. Knauer Astrid Hensel |
| author_facet | Lisa Oelschläger Paul Stahl Farnusch Kaschani Roland H. Stauber Shirley K. Knauer Astrid Hensel |
| author_sort | Lisa Oelschläger |
| collection | DOAJ |
| description | The human protease Taspase1 plays a pivotal role in developmental processes and cancerous diseases by processing critical regulators, such as the leukemia proto-oncoprotein MLL. Despite almost two decades of intense research, Taspase1’s biology is, however, still poorly understood, and so far its cellular function was not assigned to a superordinate biological pathway or a specific signaling cascade. Our data, gained by methods such as co-immunoprecipitation, LC-MS/MS and Topoisomerase II DNA cleavage assays, now functionally link Taspase1 and hormone-induced, Topoisomerase IIβ-mediated transient DNA double-strand breaks, leading to active transcription. The specific interaction with Topoisomerase IIα enhances the formation of DNA double-strand breaks that are a key prerequisite for stimulus-driven gene transcription. Moreover, Taspase1 alters the H3K4 epigenetic signature upon estrogen-stimulation by cleaving the chromatin-modifying enzyme MLL. As estrogen-driven transcription and MLL-derived epigenetic labelling are reduced upon Taspase1 siRNA-mediated knockdown, we finally characterize Taspase1 as a multifunctional co-activator of estrogen-stimulated transcription. |
| first_indexed | 2024-03-11T09:50:00Z |
| format | Article |
| id | doaj.art-49ea6af74a9d45459f84980616ea7e7d |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-11T09:50:00Z |
| publishDate | 2023-01-01 |
| publisher | MDPI AG |
| record_format | Article |
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| spelling | doaj.art-49ea6af74a9d45459f84980616ea7e7d2023-11-16T16:20:33ZengMDPI AGCells2073-44092023-01-0112336310.3390/cells12030363Taspase1 Facilitates Topoisomerase IIβ-Mediated DNA Double-Strand Breaks Driving Estrogen-Induced TranscriptionLisa Oelschläger0Paul Stahl1Farnusch Kaschani2Roland H. Stauber3Shirley K. Knauer4Astrid Hensel5Department of Molecular Biology II, Center of Medical Biotechnology (ZMB), University Duisburg-Essen, 45141 Essen, GermanyDepartment of Molecular Biology II, Center of Medical Biotechnology (ZMB), University Duisburg-Essen, 45141 Essen, GermanyAnalytics Core Facility Essen (ACE), Center of Medical Biotechnology (ZMB), University Duisburg-Essen, 45141 Essen, GermanyDepartment of Otorhinolaryngology, Molecular and Cellular Oncology, University Mainz Medical Center (UMM), 55131 Mainz, GermanyDepartment of Molecular Biology II, Center of Medical Biotechnology (ZMB), University Duisburg-Essen, 45141 Essen, GermanyDepartment of Molecular Biology II, Center of Medical Biotechnology (ZMB), University Duisburg-Essen, 45141 Essen, GermanyThe human protease Taspase1 plays a pivotal role in developmental processes and cancerous diseases by processing critical regulators, such as the leukemia proto-oncoprotein MLL. Despite almost two decades of intense research, Taspase1’s biology is, however, still poorly understood, and so far its cellular function was not assigned to a superordinate biological pathway or a specific signaling cascade. Our data, gained by methods such as co-immunoprecipitation, LC-MS/MS and Topoisomerase II DNA cleavage assays, now functionally link Taspase1 and hormone-induced, Topoisomerase IIβ-mediated transient DNA double-strand breaks, leading to active transcription. The specific interaction with Topoisomerase IIα enhances the formation of DNA double-strand breaks that are a key prerequisite for stimulus-driven gene transcription. Moreover, Taspase1 alters the H3K4 epigenetic signature upon estrogen-stimulation by cleaving the chromatin-modifying enzyme MLL. As estrogen-driven transcription and MLL-derived epigenetic labelling are reduced upon Taspase1 siRNA-mediated knockdown, we finally characterize Taspase1 as a multifunctional co-activator of estrogen-stimulated transcription.https://www.mdpi.com/2073-4409/12/3/363stimulus-triggered transcriptionhormoneshistone epigenetic labellingH3K4me3Mixed-lineage leukemia |
| spellingShingle | Lisa Oelschläger Paul Stahl Farnusch Kaschani Roland H. Stauber Shirley K. Knauer Astrid Hensel Taspase1 Facilitates Topoisomerase IIβ-Mediated DNA Double-Strand Breaks Driving Estrogen-Induced Transcription Cells stimulus-triggered transcription hormones histone epigenetic labelling H3K4me3 Mixed-lineage leukemia |
| title | Taspase1 Facilitates Topoisomerase IIβ-Mediated DNA Double-Strand Breaks Driving Estrogen-Induced Transcription |
| title_full | Taspase1 Facilitates Topoisomerase IIβ-Mediated DNA Double-Strand Breaks Driving Estrogen-Induced Transcription |
| title_fullStr | Taspase1 Facilitates Topoisomerase IIβ-Mediated DNA Double-Strand Breaks Driving Estrogen-Induced Transcription |
| title_full_unstemmed | Taspase1 Facilitates Topoisomerase IIβ-Mediated DNA Double-Strand Breaks Driving Estrogen-Induced Transcription |
| title_short | Taspase1 Facilitates Topoisomerase IIβ-Mediated DNA Double-Strand Breaks Driving Estrogen-Induced Transcription |
| title_sort | taspase1 facilitates topoisomerase iiβ mediated dna double strand breaks driving estrogen induced transcription |
| topic | stimulus-triggered transcription hormones histone epigenetic labelling H3K4me3 Mixed-lineage leukemia |
| url | https://www.mdpi.com/2073-4409/12/3/363 |
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