Greatwall depletion from Xenopus oocytes reveals a key role of the cyclin B/CDK1-PP2A-B55 balance in the coordination of meiotic events
Abstract
Meiotic progression relies on maintaining a precise balance between cyclin B/CDK1 activity and the phosphatase PP2A-B55. The latter is negatively regulated by the Greatwall kinase (Gwl). In Xenopus oocytes, we show that the loss of Gwl and the subsequent hyperactivation of PP2A-B55 severely disrupt the transition from meiosis I to meiosis II. This disruption prevents phosphorylation of both Wee1/Myt1 and the APC/C complex, thereby blocking APC/C activation. As a consequence, APC/C remains inactive during the MI-MII transition, which impairs cyclin degradation and the partial CDK1 inactivation that is normally required at this stage. Additionally, the mos-MAPK-Rsk1/2 pathway fails to activate due to insufficient Mos accumulation, thereby preventing metaphase II arrest. Finally, the lack of APC/C activation during meiosis I inhibits the degradation of its inhibitor Erp1, revealing a critical feedback loop between APC/C and Erp1. Overall, our findings reveal that Gwl is a key coordinator of both meiotic divisions, acting through dual regulation of APC/C and the Mos/MAPK/Rsk1/2 pathways by modulating PP2A-B55 activity.
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BibTeX
@misc{roque2026greatwall,
title = {{Greatwall depletion from Xenopus oocytes reveals a key role of the cyclin B/CDK1-PP2A-B55 balance in the coordination of meiotic events}},
author = {Sylvain Roque and Cedric Hassen Khodja and Célia Ben Choug and Suzanne Vigneron and Véronique Legros and Guillaume Chevreux and Benjamin Lacroix and Anna Castro and Thierry Lorca},
howpublished = {Nature Communications},
year = {2026},
month = may,
doi = {10.1101/2025.10.03.680315},
url = {https://hal.science/hal-05837239v1},
note = {CC BY 4.0},
}
RIS
TY - UNPB
TI - Greatwall depletion from Xenopus oocytes reveals a key role of the cyclin B/CDK1-PP2A-B55 balance in the coordination of meiotic events
AU - Sylvain Roque
AU - Cedric Hassen Khodja
AU - Célia Ben Choug
AU - Suzanne Vigneron
AU - Véronique Legros
AU - Guillaume Chevreux
AU - Benjamin Lacroix
AU - Anna Castro
AU - Thierry Lorca
PY - 2026
DA - 2026/05/13
PB - Nature Communications
DO - 10.1101/2025.10.03.680315
UR - https://hal.science/hal-05837239v1
AB - Meiotic progression relies on maintaining a precise balance between cyclin B/CDK1 activity and the phosphatase PP2A-B55. The latter is negatively regulated by the Greatwall kinase (Gwl). In Xenopus oocytes, we show that the loss of Gwl and the subsequent hyperactivation of PP2A-B55 severely disrupt the transition from meiosis I to meiosis II. This disruption prevents phosphorylation of both Wee1/Myt1 and the APC/C complex, thereby blocking APC/C activation. As a consequence, APC/C remains inactive during the MI-MII transition, which impairs cyclin degradation and the partial CDK1 inactivation that is normally required at this stage. Additionally, the mos-MAPK-Rsk1/2 pathway fails to activate due to insufficient Mos accumulation, thereby preventing metaphase II arrest. Finally, the lack of APC/C activation during meiosis I inhibits the degradation of its inhibitor Erp1, revealing a critical feedback loop between APC/C and Erp1. Overall, our findings reveal that Gwl is a key coordinator of both meiotic divisions, acting through dual regulation of APC/C and the Mos/MAPK/Rsk1/2 pathways by modulating PP2A-B55 activity.
SN - 2041-1723
SN - 2041-1723
ER -