Translation regulator ballet in meiotic spindle

Cormier, Patrick

doi:10.1080/15384101.2017.1304732

Cited by 3 publications

(1 citation statement)

References 7 publications

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“…Moreover, the CDK12 target CHK1 is an important component of the SAC, acting through the Aurora B kinase to prevent formation of lagging chromosomes (Kabeche et al 2018). Of note, 4E-BP1 proteins phosphorylated at T70 and S65 localize to the mitotic spindle and control spindle assembly in murine oocytes (Cormier 2017;Jansova et al 2017), which raises the possibility that CDK12 might also act directly at mitotic chromosomes. Consistent with our findings, knockdown of CCNK in prostate cancer cells was previously shown to lead to an Aurora B kinase-dependent mitotic catastrophe, characterized by spindle multipolarity and multinucleation (Schecher et al 2017).…”

Section: Discussionmentioning

confidence: 99%

CDK12 phosphorylates 4E-BP1 to enable mTORC1-dependent translation and mitotic genome stability

et al. 2019

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The RNA polymerase II (RNAPII) C-terminal domain kinase, CDK12, regulates genome stability, expression of DNA repair genes, and cancer cell resistance to chemotherapy and immunotherapy. In addition to its role in mRNA biosynthesis of DNA repair genes, we show here that CDK12 phosphorylates the mRNA 5 ′ cap-binding repressor, 4E-BP1, to promote translation of mTORC1-dependent mRNAs. In particular, we found that phosphorylation of 4E-BP1 by mTORC1 (T37 and T46) facilitates subsequent CDK12 phosphorylation at two Ser-Pro sites (S65 and T70) that control the exchange of 4E-BP1 with eIF4G at the 5 ′ cap of CHK1 and other target mRNAs. RNA immunoprecipitation coupled with deep sequencing (RIP-seq) revealed that CDK12 regulates release of 4E-BP1, and binding of eIF4G, to many mTORC1 target mRNAs, including those needed for MYC transformation. Genome-wide ribosome profiling (Ribo-seq) further identified specific CDK12 "translation-only" target mRNAs, including many mTORC1 target mRNAs as well as many subunits of mitotic and centromere/ centrosome complexes. Accordingly, confocal imaging analyses revealed severe chromosome misalignment, bridging, and segregation defects in cells deprived of CDK12 or CCNK. We conclude that the nuclear RNAPII-CTD kinase CDK12 cooperates with mTORC1, and controls a specialized translation network that is essential for mitotic chromosome stability.

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Section: Discussionmentioning

confidence: 99%

CDK12 phosphorylates 4E-BP1 to enable mTORC1-dependent translation and mitotic genome stability

et al. 2019

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Toward Multiscale Modeling of Molecular and Biochemical Events Occurring at Fertilization Time in Sea Urchins

Moundoyi¹,

Demouy²,

Panse³

et al. 2018

Results and Problems in Cell Differentiation

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We review here previous theoretical and experimental works, which aim to model major events that occur at the time of fertilization in the sea urchin. We discuss works that perform experiments and develop hypotheses that link different scales of biological systems such as the intracellular Ca concentration oscillations and the swimming behavior of sperm, the Ca wave propagation and the fertilization membrane elevation of the egg, and the mRNA translational activation and the completion of the first mitotic division of the early embryo. The aim of this review is on one hand, to highlight the value of systems biology for understanding the mechanisms associated with fertilization and early embryonic development in sea urchins. On the other hand, this review attempts to illustrate, for mathematicians and bioinformaticians, the potential that represent these molecular and cellular events for modeling clear physiological processes.

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Preantral follicle culture and oocyte quality

Heiligentag

Eichenlaub-Ritter

2018

Reprod. Fertil. Dev.

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The formation of high-quality oocytes depends on complex stage-specific interactions between the germ cell and the somatic compartment involving endocrine, paracrine, and autocrine regulation. Cooperativity in bidirectional signalling and metabolism in response to factors in the microenvironment drive growth, proliferation, cell cycle regulation, spindle formation and the establishment of epigenetic marks in oocytes. This is essential to ensure faithful chromosome segregation and to achieve high oocyte quality, with far-reaching consequences for embryo survival, development and the health of offspring. Oocytes reach developmental capacity throughout early meiotic stages up to full growth and acquisition of nuclear and cytoplasmic maturational competence during folliculogenesis. Improved preantral follicle culture in which ideally intimate contacts between oocyte and somatic cells are retained provides unique opportunities to assess the effects of microenvironment, growth factors, hormones, cryopreservation and environmental exposure on folliculogenesis and oocyte quality. An optimised follicle culture can contribute to the generation of high-quality oocytes for use in fertility preservation in cancer patients, animal breeding and the preservation of endangered species. The past decade has brought about major advances in follicle culture from different species. Recent advances in preantral follicle culture are discussed to assess the effects of environment, adverse exposure, cryopreservation and age on oocyte quality.

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Translation regulator ballet in meiotic spindle

Cited by 3 publications

References 7 publications

CDK12 phosphorylates 4E-BP1 to enable mTORC1-dependent translation and mitotic genome stability

CDK12 phosphorylates 4E-BP1 to enable mTORC1-dependent translation and mitotic genome stability

Toward Multiscale Modeling of Molecular and Biochemical Events Occurring at Fertilization Time in Sea Urchins

Preantral follicle culture and oocyte quality

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