FBXO38 Ubiquitin Ligase Controls Centromere Integrity via ZXDA/B Stability

0559232 - ÚMG 2023 RIV CH eng J - Journal Article
Dibus, Nikol - Kořínek, Vladimír - Čermák, Lukáš
FBXO38 Ubiquitin Ligase Controls Centromere Integrity via ZXDA/B Stability.
Frontiers in Cell and Developmental Biology. Roč. 10, June (2022), č. článku 929288. ISSN 2296-634X. E-ISSN 2296-634X
R&D Projects: GA ČR(CZ) GA18-27408S; GA MZd NU21-08-00312; GA MŠMT(CZ) LM2018131
Institutional support: RVO:68378050
Keywords : proteasome * ubiquitin ligase * protein degradation * cullin * zinc finger protein * centromere
OECD category: Cell biology
Impact factor: 5.5, year: 2022
Method of publishing: Open access
https://www.frontiersin.org/articles/10.3389/fcell.2022.929288/full

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.
Permanent Link: https://hdl.handle.net/11104/0332882