Cyclin B3 implements timely vertebrate oocyte arrest for fertilization

Bouftas, Nora; Schneider, Lena; Halder, Marc; Demmig, Rebecca; Baack, Martina; Cladière, Damien; Walter, Melanie; Abdallah, Hiba Al; Kleinhempel, Camilla; Messaritaki, Ria; Müller, Janina; Passarelli, Francesca; Wehrle, Patrick; Heim, Andreas; Wassmann, Katja; Mayer, Thomas

doi:10.1016/j.devcel.2022.09.005

Cited by 12 publications

(28 citation statements)

References 48 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…For CSF preparation, frogs were primed with injection of 20 U human chorionic gonadotropin (hCG) 3 to 14 days previous to injection of 500 U hCG to induce egg laying according to approved proposal (file number: 35-9185.81/G-22/081). Further CSF preparation was performed by step wise centrifugation of dejelled eggs (described in detail in Bouftas et al 2022).…”

Section: Xenopus Laevis Stage VI Oocytes and Csf Extractmentioning

confidence: 99%

“…Fertilization triggers degradation of XErp1/Emi2, thereby resulting in APC/C activation and, hence, in exit from MII (Hansen et al , 2006; Liu et al , 2006; Rauh et al , 2005). Recently, we could dissect cyclin B3’s essential function in female meiosis by demonstrating that it targets the APC/C inhibitor XErp1/Emi2 for proteasomal degradation in meiosis I (Bouftas et al , 2022). This mechanism, which is conserved from frog to mouse and includes Plk1 (Polo-like kinase 1), is essential to keep the levels of XErp1/Emi2 during meiosis I below the threshold critical for APC/C inhibition (Bouftas et al ., 2022; Meng et al , 2020).…”

Section: Introductionmentioning

confidence: 99%

“…Recently, we could dissect cyclin B3’s essential function in female meiosis by demonstrating that it targets the APC/C inhibitor XErp1/Emi2 for proteasomal degradation in meiosis I (Bouftas et al , 2022). This mechanism, which is conserved from frog to mouse and includes Plk1 (Polo-like kinase 1), is essential to keep the levels of XErp1/Emi2 during meiosis I below the threshold critical for APC/C inhibition (Bouftas et al ., 2022; Meng et al , 2020). Destruction of cyclin B3 during exit from MI allows XErp1/Emi2 accumulation resulting in APC/C inhibition essential for entry into MII.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

A phosphate-binding pocket in cyclin B3 is essential for XErp1/ Emi2 degradation in meiosis I

Demmig,

Schäfer,

Johannes

et al. 2024

Preprint

Self Cite

View full text Add to dashboard Cite

To ensure the correct euploid state of embryos, it is essential that vertebrate oocytes await fertilization arrested at metaphase of meiosis II. This MII arrest is mediated by XErp1/Emi2, which inhibits the ubiquitin ligase APC/C (anaphase-promoting complex/cyclosome). Cyclin B3 in complex with Cdk1 (cyclin-dependent kinase 1) is essential to prevent an untimely arrest of vertebrate oocytes in meiosis I by targeting XErp1/Emi2 for degradation. Yet, the molecular mechanism of XErp1/Emi2 degradation in MI is not well understood. Here, by combining TRIM-Away in oocytes with egg extract and in vitro studies, we demonstrate that a hitherto unknown phosphate-binding pocket in cyclin B3 is essential for efficient XErp1/Emi2 degradation in meiosis I. This pocket enables Cdk1/cyclin B3 to bind pre-phosphorylated XErp1/Emi2 facilitating further phosphorylation events, which ultimately target XErp1/Emi2 for degradation in a Plk1 (Polo-like kinase 1) dependent manner. Key elements of this degradative mechanism are conserved in frog and mouse. Our studies identify a novel, evolutionarily conserved determinant of Cdk/cyclin substrate specificity essential to prevent an untimely oocyte arrest at meiosis I with catastrophic consequences upon fertilization.

show abstract

Section: Xenopus Laevis Stage VI Oocytes and Csf Extractmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

A phosphate-binding pocket in cyclin B3 is essential for XErp1/ Emi2 degradation in meiosis I

Demmig,

Schäfer,

Johannes

et al. 2024

Preprint

Self Cite

View full text Add to dashboard Cite

show abstract

“…Elle est présente tout au long de la méiose I, puis dégradée après l'anaphase de méiose I par un mécanisme impliquant le motif d'ubiquitination par l'APC (D-box), commun aux cyclines B [2,5]. En revanche, elle ne s'accumule pas en méiose II [6]. Lorsqu'elle est exprimée artificiellement à contretemps dans les ovocytes de souris bloqués en métaphase II, la cycline B3 déclenche l'anaphase de méiose II sans fécondation [5,6].…”

Section: La Cycline B3 Verrou De La Méiose Femelle En Attendant La Fé...unclassified

“…En revanche, elle ne s'accumule pas en méiose II [6]. Lorsqu'elle est exprimée artificiellement à contretemps dans les ovocytes de souris bloqués en métaphase II, la cycline B3 déclenche l'anaphase de méiose II sans fécondation [5,6]. La dérégulation de la cycline B3 a donc des effets biologiques divergents de ceux décrits pour les cyclines B1/B2, dont la surexpression bloque l'ovocyte en métaphase I et dont l'invalidation inhibe la progression en méiose II [1].…”

Section: La Cycline B3 Verrou De La Méiose Femelle En Attendant La Fé...unclassified

La cycline B3, verrou de la méiose femelle en attendant la fécondation

Dupré

Wassmann

2023

Med Sci (Paris)

Self Cite

View full text Add to dashboard Cite

A phosphate-binding pocket in cyclin B3 is essential for XErp1/Emi2 degradation in meiosis I

Schunk,

Halder,

Schäfer

et al. 2025

EMBO Rep

View full text Add to dashboard Cite

To ensure the correct euploid state of embryos, it is essential that vertebrate oocytes await fertilization arrested at metaphase of meiosis II. This MII arrest is mediated by XErp1/Emi2, which inhibits the ubiquitin ligase APC/C (anaphase-promoting complex/cyclosome). Cyclin B3 in complex with Cdk1 (cyclin-dependent kinase 1) is essential to prevent an untimely arrest of vertebrate oocytes in meiosis I by targeting XErp1/Emi2 for degradation. Yet, the molecular mechanism of XErp1/Emi2 degradation in MI is not well understood. Here, by combining TRIM-Away in oocytes with egg extract and in vitro studies, we demonstrate that a hitherto unknown phosphate-binding pocket in cyclin B3 is essential for efficient XErp1/Emi2 degradation in meiosis I. This pocket enables Cdk1/cyclin B3 to bind pre-phosphorylated XErp1/Emi2 facilitating further phosphorylation events, which ultimately target XErp1/Emi2 for degradation in a Plk1- (Polo-like kinase 1) dependent manner. Key elements of this degradative mechanism are conserved in frog and mouse. Our studies identify a novel, evolutionarily conserved determinant of Cdk/cyclin substrate specificity essential to prevent an untimely oocyte arrest at meiosis I with catastrophic consequences upon fertilization.

show abstract

Cyclin B3 implements timely vertebrate oocyte arrest for fertilization

Cited by 12 publications

References 48 publications

A phosphate-binding pocket in cyclin B3 is essential for XErp1/ Emi2 degradation in meiosis I

A phosphate-binding pocket in cyclin B3 is essential for XErp1/ Emi2 degradation in meiosis I

La cycline B3, verrou de la méiose femelle en attendant la fécondation

A phosphate-binding pocket in cyclin B3 is essential for XErp1/Emi2 degradation in meiosis I

Contact Info

Product

Resources

About