期刊
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
卷 10, 期 -, 页码 -出版社
FRONTIERS MEDIA SA
DOI: 10.3389/fcell.2022.929288
关键词
proteasome; ubiquitin ligase; protein degradation; cullin; zinc finger protein; centromere
资金
- Czech Science Foundation [18-27408S]
- Czech Academy of Sciences
- Marie Sklodowska-Curie Fellowship
- Czech Health Research Council [NU21-08-00312]
- ELIXIR CZ research infrastructure (MEYS) [LM2018131]
- project National Institute for Cancer Research (Programme EXCELES) - European Union-Next Generation EU [LX22NPO5102]
The gene encoding FBXO38, an E3 ubiquitin ligase substrate receptor, has been found to be associated with various diseases. The study shows that FBXO38 controls the stability of ZXDA/B proteins through ubiquitination and proteasome-dependent degradation. These ZXDA/B proteins are involved in the regulation of chromatin-associated CENP-B protein levels, and their inappropriate stabilization leads to upregulation of CENP-A and CENP-B in centromeric chromatin.
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.
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