Cyclin dependent kinase 1 (CDK1) has been primarily identified as a key cell cycle regulator in both mitosis and meiosis. Recently, an extramitotic function of CDK1 emerged when evidence was found that CDK1 is involved in many cellular events that are essential for cell proliferation and survival. In this review we summarize the involvement of CDK1 in the initiation and elongation steps of protein synthesis in the cell. During its activation, CDK1 influences the initiation of protein synthesis, promotes the activity of specific translational initiation factors and affects the functioning of a subset of elongation factors. Our review provides insights into gene expression regulation during the transcriptionally silent M-phase and describes quantitative and qualitative translational changes based on the extramitotic role of the cell cycle master regulator CDK1 to optimize temporal synthesis of proteins to sustain the division-related processes: mitosis and cytokinesis.

• Klíčová slova
• 4E-BP1, CDK1, M-phase, mRNA, mTOR, translation,
• MeSH
• buněčný cyklus genetika   fyziologie   MeSH
• lidé MeSH
• messenger RNA genetika   metabolismus   MeSH
• proteinkinasa CDC2 genetika   metabolismus   MeSH
• proteiny buněčného cyklu genetika   metabolismus   MeSH
• TOR serin-threoninkinasy genetika   metabolismus   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Názvy látek
• messenger RNA MeSH
• proteinkinasa CDC2 MeSH
• proteiny buněčného cyklu MeSH
• TOR serin-threoninkinasy MeSH

In the absence of transcription, the regulation of gene expression in oocytes is controlled almost exclusively at the level of transcriptome and proteome stabilization, and translation. A subset of maternal transcripts is stored in a translationally dormant state in the oocyte, and temporally driven translation of specific mRNAs propel meiotic progression, oocyte-to-embryo transition and early embryo development. We identified Ank2.3 as the only transcript variant present in the mouse oocyte and discovered that it is translated after nuclear envelope breakdown. Here we show that Ank2.3 mRNA is localized in higher concentration in the oocyte nucleoplasm and, after nuclear envelope breakdown, in the newly forming spindle where its translation occurs. Furthermore, we reveal that Ank2.3 mRNA contains an oligo-pyrimidine motif at 5'UTR that predetermines its translation through a cap-dependent pathway. Lastly, we show that prevention of ANK2 translation leads to abnormalities in oocyte cytokinesis.

• MeSH
• ankyriny genetika   metabolismus   MeSH
• časoprostorová analýza * MeSH
• cytokineze * MeSH
• embryo savčí cytologie   fyziologie   MeSH
• meióza * MeSH
• messenger RNA genetika   metabolismus   MeSH
• myši MeSH
• oocyty cytologie   fyziologie   MeSH
• oogeneze MeSH
• vývojová regulace genové exprese * MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• Ank2 protein, mouse MeSH Prohlížeč
• ankyriny MeSH
• messenger RNA MeSH

The tight correlation between mRNA distribution and subsequent protein localization and function indicate a major role for mRNA localization within the cell. RNA localization, followed by local translation, presents a mechanism for spatial and temporal gene expression regulation utilized by various cell types. However, little is known about mRNA localization and translation in the mammalian oocyte and early embryo. Importantly, fully-grown oocyte becomes transcriptionally inactive and only utilizes transcripts previously synthesized and stored during earlier development. We discovered an abundant RNA population in the oocyte and early embryo nucleus together with RNA binding proteins. We also characterized specific ribosomal proteins, which contribute to translation in the oocyte and embryo. By applying selected markers to mouse and human oocytes, we found that there might be a similar mechanism of RNA metabolism in both species. In conclusion, we visualized the localization of RNAs and translation machinery in the oocyte, that could shed light on this terra incognita of these unique cell types in mouse and human.

• MeSH
• embryo savčí metabolismus   ultrastruktura   MeSH
• kultivované buňky MeSH
• lidé MeSH
• messenger RNA analýza   genetika   MeSH
• myši MeSH
• oocyty metabolismus   ultrastruktura   MeSH
• proteiny vázající RNA analýza   genetika   MeSH
• proteosyntéza * MeSH
• transkriptom MeSH
• vývojová regulace genové exprese * MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• messenger RNA MeSH
• proteiny vázající RNA MeSH

Although the involvement of the extracellular signal-regulated kinases 1 and 2 (ERK1/2) pathway in the regulation of cytostatic factor (CSF) activity; as well as in microtubules organization during meiotic maturation of oocytes; has already been described in detail; rather less attention has been paid to the role of ERK1/2 in the regulation of mRNA translation. However; important data on the role of ERK1/2 in translation during oocyte meiosis have been documented. This review focuses on recent findings regarding the regulation of translation and the role of ERK1/2 in this process in the meiotic cycle of mammalian oocytes. The specific role of ERK1/2 in the regulation of mammalian target of rapamycin (mTOR); eukaryotic translation initiation factor 4E (eIF4E) and cytoplasmic polyadenylation element binding protein 1 (CPEB1) activity is addressed along with additional focus on the other key players involved in protein translation.

• Klíčová slova
• CPEB1, ERK1/2, MAP kinase, eIF4E, mTOR, oocyte, translation,
• MeSH
• cytoplazma genetika   metabolismus   MeSH
• eukaryotický iniciační faktor 4E metabolismus   MeSH
• faktory štěpení a polyadenylace mRNA metabolismus   MeSH
• fosfatidylinositol-3-kinasy metabolismus   MeSH
• lidé MeSH
• meióza * MeSH
• messenger RNA genetika   metabolismus   MeSH
• mitogenem aktivovaná proteinkinasa 1 metabolismus   MeSH
• mitogenem aktivovaná proteinkinasa 3 metabolismus   MeSH
• mitogenem aktivované proteinkinasy metabolismus   MeSH
• oocyty metabolismus   MeSH
• polyadenylace MeSH
• proteosyntéza * MeSH
• signální transdukce MeSH
• TOR serin-threoninkinasy metabolismus   MeSH
• vazba proteinů MeSH
• vývojová regulace genové exprese MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• eukaryotický iniciační faktor 4E MeSH
• faktory štěpení a polyadenylace mRNA MeSH
• messenger RNA MeSH
• mitogenem aktivovaná proteinkinasa 1 MeSH
• mitogenem aktivovaná proteinkinasa 3 MeSH
• mitogenem aktivované proteinkinasy MeSH
• TOR serin-threoninkinasy MeSH

Fully grown mammalian oocytes utilize transcripts synthetized and stored during earlier development. RNA localization followed by a local translation is a mechanism responsible for the regulation of spatial and temporal gene expression. Here we show that the mouse oocyte contains 3 forms of cap-dependent translational repressor expressed on the mRNA level: 4E-BP1, 4E-BP2 and 4E-BP3. However, only 4E-BP1 is present as a protein in oocytes, it becomes inactivated by phosphorylation after nuclear envelope breakdown and as such it promotes cap-dependent translation after NEBD. Phosphorylation of 4E-BP1 can be seen in the oocytes after resumption of meiosis but it is not detected in the surrounding cumulus cells, indicating that 4E-BP1 promotes translation at a specific cell cycle stage. Our immunofluorescence analyses of 4E-BP1 in oocytes during meiosis I showed an even localization of global 4E-BP1, as well as of its 4E-BP1 (Thr37/46) phosphorylated form. On the other hand, 4E-BP1 phosphorylated on Ser65 is localized at the spindle poles, and 4E-BP1 phosphorylated on Thr70 localizes on the spindle. We further show that the main positive regulators of 4E-BP1 phosphorylation after NEBD are mTOR and CDK1 kinases, but not PLK1 kinase. CDK1 exerts its activity toward 4E-BP1 phosphorylation via phosphorylation and activation of mTOR. Moreover, both CDK1 and phosphorylated mTOR co-localize with 4E-BP1 phosphorylated on Thr70 on the spindle at the onset of meiotic resumption. Expression of the dominant negative 4E-BP1 mutant adversely affects translation and results in spindle abnormality. Taken together, our results show that the phosphorylation of 4E-BP1 promotes translation at the onset of meiosis to support the spindle assembly and suggest an important role of CDK1 and mTOR kinases in this process. We also show that the mTOR regulatory pathway is present in human oocytes and is likely to function in a similar way as in mouse oocytes.

• Klíčová slova
• 4E-BP1, CDK1, cumulus cells, kinase, mRNA, mTOR, meiosis, oocyte, spindle, translation,
• MeSH
• adaptorové proteiny signální transdukční MeSH
• aparát dělícího vřeténka genetika   MeSH
• buněčný cyklus genetika   MeSH
• eukaryotické iniciační faktory MeSH
• fosfoproteiny genetika   metabolismus   MeSH
• fosforylace MeSH
• lidé MeSH
• myši MeSH
• oocyty růst a vývoj   metabolismus   MeSH
• proteinkinasa CDC2 genetika   MeSH
• proteiny buněčného cyklu MeSH
• proteosyntéza MeSH
• TOR serin-threoninkinasy genetika   MeSH
• transportní proteiny genetika   metabolismus   MeSH
• vývojová regulace genové exprese MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• adaptorové proteiny signální transdukční MeSH
• Eif4ebp1 protein, mouse MeSH Prohlížeč
• eukaryotické iniciační faktory MeSH
• fosfoproteiny MeSH
• mTOR protein, mouse MeSH Prohlížeč
• proteinkinasa CDC2 MeSH
• proteiny buněčného cyklu MeSH
• TOR serin-threoninkinasy MeSH
• transportní proteiny MeSH