FBXO38 Ubiquitin Ligase Controls Centromere Integrity via ZXDA/B Stability
Alterations in the gene encoding the E3 ubiquitin ligase substrate receptor FBXO38 have been associated with several diseases, including early-onset motor neuronopathy. However, the cellular processes affected by the enzymatic action of FBXO38 are not yet known. Here, we identify the zinc finger pro...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-06-01
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| Series: | Frontiers in Cell and Developmental Biology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fcell.2022.929288/full |
| _version_ | 1797995108673519616 |
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| author | Nikol Dibus Vladimir Korinek Lukas Cermak |
| author_facet | Nikol Dibus Vladimir Korinek Lukas Cermak |
| author_sort | Nikol Dibus |
| collection | DOAJ |
| description | Alterations in the gene encoding the E3 ubiquitin ligase substrate receptor FBXO38 have been associated with several diseases, including early-onset motor neuronopathy. However, the cellular processes affected by the enzymatic action of FBXO38 are not yet known. Here, we identify the zinc finger proteins ZXDA/B as its interaction partners. FBXO38 controls the stability of ZXDA/B proteins via ubiquitination and proteasome-dependent degradation. We show that ZXDA/B proteins associate with the centromeric protein CENP-B and that the interaction between ZXDA/B and FBXO38 or CENP-B is mutually exclusive. Functionally, ZXDA/B factors control the protein level of chromatin-associated CENP-B. Furthermore, their inappropriate stabilization leads to upregulation of CENP-A and CENP-B positive centromeric chromatin. Thus we demonstrate a previously unknown role of cullin-dependent protein degradation in the control of centromeric chromatin integrity. |
| first_indexed | 2024-04-11T09:56:11Z |
| format | Article |
| id | doaj.art-521401f1bdbd49c28a46501dd9305f1f |
| institution | Directory Open Access Journal |
| issn | 2296-634X |
| language | English |
| last_indexed | 2024-04-11T09:56:11Z |
| publishDate | 2022-06-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cell and Developmental Biology |
| spelling | doaj.art-521401f1bdbd49c28a46501dd9305f1f2022-12-22T04:30:36ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2022-06-011010.3389/fcell.2022.929288929288FBXO38 Ubiquitin Ligase Controls Centromere Integrity via ZXDA/B StabilityNikol Dibus0Vladimir Korinek1Lukas Cermak2Laboratory of Cancer Biology, Institute of Molecular Genetics of the Czech Academy of Sciences, Vestec, CzechiaLaboratory of Cell and Developmental Biology, Institute of Molecular Genetics of the Czech Academy of Sciences, Prague, CzechiaLaboratory of Cancer Biology, Institute of Molecular Genetics of the Czech Academy of Sciences, Vestec, CzechiaAlterations in the gene encoding the E3 ubiquitin ligase substrate receptor FBXO38 have been associated with several diseases, including early-onset motor neuronopathy. However, the cellular processes affected by the enzymatic action of FBXO38 are not yet known. Here, we identify the zinc finger proteins ZXDA/B as its interaction partners. FBXO38 controls the stability of ZXDA/B proteins via ubiquitination and proteasome-dependent degradation. We show that ZXDA/B proteins associate with the centromeric protein CENP-B and that the interaction between ZXDA/B and FBXO38 or CENP-B is mutually exclusive. Functionally, ZXDA/B factors control the protein level of chromatin-associated CENP-B. Furthermore, their inappropriate stabilization leads to upregulation of CENP-A and CENP-B positive centromeric chromatin. Thus we demonstrate a previously unknown role of cullin-dependent protein degradation in the control of centromeric chromatin integrity.https://www.frontiersin.org/articles/10.3389/fcell.2022.929288/fullproteasomeubiquitin ligaseprotein degradationcullinzinc finger proteincentromere |
| spellingShingle | Nikol Dibus Vladimir Korinek Lukas Cermak FBXO38 Ubiquitin Ligase Controls Centromere Integrity via ZXDA/B Stability Frontiers in Cell and Developmental Biology proteasome ubiquitin ligase protein degradation cullin zinc finger protein centromere |
| title | FBXO38 Ubiquitin Ligase Controls Centromere Integrity via ZXDA/B Stability |
| title_full | FBXO38 Ubiquitin Ligase Controls Centromere Integrity via ZXDA/B Stability |
| title_fullStr | FBXO38 Ubiquitin Ligase Controls Centromere Integrity via ZXDA/B Stability |
| title_full_unstemmed | FBXO38 Ubiquitin Ligase Controls Centromere Integrity via ZXDA/B Stability |
| title_short | FBXO38 Ubiquitin Ligase Controls Centromere Integrity via ZXDA/B Stability |
| title_sort | fbxo38 ubiquitin ligase controls centromere integrity via zxda b stability |
| topic | proteasome ubiquitin ligase protein degradation cullin zinc finger protein centromere |
| url | https://www.frontiersin.org/articles/10.3389/fcell.2022.929288/full |
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