Kalidass, Manikandan and Jarubula, Venkata Ganesh and Ratnikava, Maryia and Chandra, Jothipriya Ramakrishnan and Le Goff, Samuel and Probst, Aline and Esposito, Silvia and Grasser, Klaus D. and Bruckmann, Astrid and Gagneux, Jerome F. and Prosee, Reinier F. and Rutten, Twan and Schubert, Veit and Demidov, Dmitri and Lechner, Esther and Steiner, Florian A. and Genschik, Pascal and Lermontova, Inna (2025) Ubiquitin-dependent proteolysis of KNL2 driven by APC/CCDC20 is critical for centromere integrity and mitotic fidelity. PLANT CELL, 37 (7): koaf164. ISSN 1040-4651, 1532-298X
Full text not available from this repository. (Request a copy)Abstract
Kinetochores are large protein complexes that serve as attachment sites for spindle microtubules, ensuring proper chromosome segregation during cell division. KINETOCHORE NULL2 (alpha KNL2) is a key kinetochore protein required for the incorporation of the centromeric histone variant CENH3. The precise regulation of alpha KNL2 levels is crucial, but the molecular mechanisms controlling this process remain largely unexplored. In this study, we demonstrated that the Anaphase-Promoting Complex/Cyclosome (APC/C) mediates the ubiquitin-dependent proteolysis of alpha KNL2 during mitosis. Our findings revealed that alpha KNL2 accumulates in the presence of 26S proteasome inhibitors, and our yeast 2-hybrid and proteomic screens showed that proteins from the ubiquitin-proteasome pathway interact with KNL2 in Arabidopsis (Arabidopsis thaliana) and nematode (Caenorhabditis elegans). Arabidopsis alpha KNL2 directly interacts with Anaphase-Promoting Complex subunit 10 (APC10) and Cell Division Cycle 20.1 (CDC20.1), 2 substrate recognition components of the APC/C. RNAi-mediated depletion of APC/C resulted in the accumulation and mislocalization of endogenous alpha KNL2. Additionally, mutation or deletion of the D-box1 region, or substitution of residues K336 and K339, impaired alpha KNL2 degradation. The expression of a proteasome-resistant alpha KNL2 variant in planta caused severe defects in growth, fertility, and mitotic division. These findings show that APC/CCDC20-mediated degradation of alpha KNL2 is critical for proper kinetochore function and centromere integrity. Controlled degradation of the kinetochore protein KNL2 during cell division preserves genome stability and promotes normal plant growth and development.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | ANAPHASE-PROMOTING COMPLEX; CENP-A; HISTONE H3; ARABIDOPSIS; CHROMATIN; DEGRADATION; PROTEINS; FAMILY; DESTRUCTION; PROTEASOME; |
| Subjects: | 500 Science > 540 Chemistry & allied sciences 500 Science > 570 Life sciences |
| Divisions: | Biology, Preclinical Medicine > Institut für Pflanzenwissenschaften > Lehrstuhl für Zellbiologie und Pflanzenphysiologie (Prof. Dr. Klaus Grasser) Biology, Preclinical Medicine > Institut für Biochemie, Genetik und Mikrobiologie > Lehrstuhl für Biochemie I |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 28 Jul 2026 11:38 |
| Last Modified: | 28 Jul 2026 11:38 |
| URI: | https://pred.uni-regensburg.de/id/eprint/67273 |
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