A serine/threonine-specific protein kinase B (PKB), also known as Akt, is a key factor in the phosphoinositide 3-kinase (PI3K)/Akt signaling pathway that regulates cell survival, metabolism and proliferation. Akt phosphorylates many downstream specific substrates, which subsequently control the nuclear envelope breakdown (NEBD), centrosome maturation, spindle assembly, chromosome segregation, and cytokinesis. In vertebrates, Akt is also an important player during oogenesis and preimplantation development. In the signaling pathways regulating mRNA translation, Akt is involved in the control of mammalian target of rapamycin complex 1 (mTORC1) and thereby regulates the activity of a translational repressor, the eukaryotic initiation factor 4E (eIF4E) binding protein 1 (4E-BP1). In this review, we summarize the functions of Akt in mitosis, meiosis and early embryonic development. Additionally, the role of Akt in the regulation of mRNA translation is addressed with respect to the significance of this process during early development.

• Klíčová slova
• Akt kinase, early embryo, mRNA translation, mTORC1, meiosis, mitosis, oocyte, spindle,
• MeSH
• 1-fosfatidylinositol-3-kinasa metabolismus   MeSH
• embryonální vývoj MeSH
• fosfatidylinositol-3-kinasy * metabolismus   MeSH
• fosfoproteiny metabolismus   MeSH
• fosforylace genetika   MeSH
• oocyty metabolismus   MeSH
• oogeneze MeSH
• protein-serin-threoninkinasy metabolismus   MeSH
• protoonkogenní proteiny c-akt * metabolismus   MeSH
• savci metabolismus   MeSH
• signální transdukce MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Názvy látek
• 1-fosfatidylinositol-3-kinasa MeSH
• fosfatidylinositol-3-kinasy * MeSH
• fosfoproteiny MeSH
• protein-serin-threoninkinasy MeSH
• protoonkogenní proteiny c-akt * MeSH

Cells are equipped with a diverse network of signaling and regulatory proteins that function as cell cycle regulators and checkpoint proteins to ensure the proper progression of cell division. A key regulator of cell division is polo-like kinase 1 (PLK1), a member of the serine/threonine kinase family that plays an important role in regulating the mitotic and meiotic cell cycle. The phosphorylation of specific substrates mediated by PLK1 controls nuclear envelope breakdown (NEBD), centrosome maturation, proper spindle assembly, chromosome segregation, and cytokinesis. In mammalian oogenesis, PLK1 is essential for resuming meiosis before ovulation and for establishing the meiotic spindle. Among other potential roles, PLK1 regulates the localized translation of spindle-enriched mRNAs by phosphorylating and thereby inhibiting the translational repressor 4E-BP1, a downstream target of the mTOR (mammalian target of rapamycin) pathway. In this review, we summarize the functions of PLK1 in mitosis, meiosis, and cytokinesis and focus on the role of PLK1 in regulating mRNA translation. However, knowledge of the role of PLK1 in the regulation of meiosis remains limited.

• Klíčová slova
• PLK1, mRNA translation, meiosis, mitosis, oocytes, polo-like kinase 1, spindle,
• MeSH
• lidé MeSH
• meióza MeSH
• mitóza MeSH
• polo-like kinasa 1 MeSH
• protein-serin-threoninkinasy * metabolismus   MeSH
• proteiny buněčného cyklu * metabolismus   MeSH
• protoonkogenní proteiny metabolismus   MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Názvy látek
• protein-serin-threoninkinasy * MeSH
• proteiny buněčného cyklu * MeSH
• protoonkogenní proteiny MeSH

In mammalian females, oocytes are stored in the ovary and meiosis is arrested at the diplotene stage of prophase I. When females reach puberty oocytes are selectively recruited in cycles to grow, overcome the meiotic arrest, complete the first meiotic division and become mature (ready for fertilization). At a molecular level, the master regulator of prophase I arrest and meiotic resumption is the maturation-promoting factor (MPF) complex, formed by the active form of cyclin dependent kinase 1 (CDK1) and Cyclin B1. However, we still do not have complete information regarding the factors implicated in MPF activation. In this study we document that out of three mammalian serum-glucocorticoid kinase proteins (SGK1, SGK2, SGK3), mouse oocytes express only SGK1 with a phosphorylated (active) form dominantly localized in the nucleoplasm. Further, suppression of SGK1 activity in oocytes results in decreased CDK1 activation via the phosphatase cell division cycle 25B (CDC25B), consequently delaying or inhibiting nuclear envelope breakdown. Expression of exogenous constitutively active CDK1 can rescue the phenotype induced by SGK1 inhibition. These findings bring new insights into the molecular pathways acting upstream of MPF and a better understanding of meiotic resumption control by presenting a new key player SGK1 in mammalian oocytes.

• Klíčová slova
• CDK1, MPF, Meiosis, Nuclear envelope breakdown, Oocyte, SGK1,
• MeSH
• faktor podporující zrání * metabolismus   MeSH
• kontrolní body buněčného cyklu MeSH
• meióza MeSH
• myši MeSH
• oocyty metabolismus   MeSH
• profáze meiózy I MeSH
• protein-serin-threoninkinasy genetika   MeSH
• proteiny bezprostředně časné * genetika   metabolismus   MeSH
• savci metabolismus   MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• faktor podporující zrání * MeSH
• protein-serin-threoninkinasy MeSH
• proteiny bezprostředně časné * MeSH
• serum-glucocorticoid regulated kinase MeSH Prohlížeč

Mammalian oocytes are arrested at prophase I until puberty when luteinizing hormone (LH) induces resumption of meiosis of follicle-enclosed oocytes. Resumption of meiosis is tightly coupled with regulating cyclin-dependent kinase 1 (CDK1) activity. Prophase I arrest depends on inhibitory phosphorylation of CDK1 and anaphase-promoting complex-(APC-CDH1)-mediated regulation of cyclin B levels. Prophase I arrest is maintained by endogenously produced cyclic adenosine monophosphate (cAMP), which activates protein kinase A (PKA) that in turn phosphorylates (and activates) the nuclear kinase WEE2. In addition, PKA-mediated phosphorylation of the phosphatase CDC25B results in its cytoplasmic retention. The combined effect maintains low levels of CDK1 activity that are not sufficient to initiate resumption of meiosis. LH triggers synthesis of epidermal growth factor-like factors in mural granulosa cells and leads to reduced cGMP transfer from cumulus cells to oocytes via gap junctions that couple the two cell types. cGMP inhibits oocyte phosphodiesterase 3A (PDE3A) and a decline in oocyte cGMP results in increased PDE3A activity. The ensuing decrease in oocyte cAMP triggers maturation by alleviating the aforementioned phosphorylations of WEE2 and CDC25B. As a direct consequence CDC25B translocates into the nucleus. The resulting activation of CDK1 also promotes extrusion of WEE2 from the nucleus thereby providing a positive amplification mechanism for CDK1 activation. Other kinases, e.g. protein kinase B, Aurora kinase A and polo-like kinase 1, also participate in resumption of meiosis. Mechanisms governing meiotic prophase I arrest and resumption of meiosis share common features with DNA damage-induced mitotic G2-checkpoint arrest and checkpoint recovery, respectively. These common features include CDC14B-dependent activation of APC-CDH1 in prophase I arrested oocytes or G2-arrested somatic cells, and CDC25B-dependent cell cycle resumption in both oocytes and somatic cells.

• MeSH
• AMP cyklický metabolismus   MeSH
• anafázi podporující komplex MeSH
• Cdh1 proteiny MeSH
• cyklin B1 metabolismus   MeSH
• epidermální růstový faktor metabolismus   MeSH
• G2 fáze * MeSH
• inhibiční proteiny cyklin-dependentních kinas metabolismus   MeSH
• komplexy ubikvitinligas metabolismus   MeSH
• meióza * MeSH
• metafáze MeSH
• myši MeSH
• oocyty metabolismus   MeSH
• oogeneze * MeSH
• profáze meiózy I MeSH
• proliferace buněk * MeSH
• proteiny buněčného cyklu metabolismus   MeSH
• signální transdukce * MeSH
• věkové faktory MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Research Support, N.I.H., Extramural MeSH
• Názvy látek
• AMP cyklický MeSH
• anafázi podporující komplex MeSH
• Ccnb1 protein, mouse MeSH Prohlížeč
• Cdh1 proteiny MeSH
• cyklin B1 MeSH
• epidermální růstový faktor MeSH
• Fzr1 protein, mouse MeSH Prohlížeč
• inhibiční proteiny cyklin-dependentních kinas MeSH
• komplexy ubikvitinligas MeSH
• proteiny buněčného cyklu MeSH

Aurora kinase A (AURKA), which is a centrosome-localized serine/threonine kinase crucial for cell cycle control, is critically involved in centrosome maturation and spindle assembly in somatic cells. Active T288 phosphorylated AURKA localizes to the centrosome in the late G(2) and also spreads to the minus ends of mitotic spindle microtubules. AURKA activates centrosomal CDC25B and recruits cyclin B1 to centrosomes. We report here functions for AURKA in meiotic maturation of mouse oocytes, which is a model system to study the G(2) to M transition. Whereas AURKA is present throughout the entire GV-stage oocyte with a clear accumulation on microtubule organizing centers (MTOC), active AURKA becomes entirely localized to MTOCs shortly before germinal vesicle breakdown. In contrast to somatic cells in which active AURKA is present at the centrosomes and minus ends of microtubules, active AURKA is mainly located on MTOCs at metaphase I (MI) in oocytes. Inhibitor studies using Roscovitine (CDK1 inhibitor), LY-294002 (PI3K inhibitor) and SH-6 (PKB inhibitor) reveal that activation of AURKA localized on MTOCs is independent on PI3K-PKB and CDK1 signaling pathways and MOTC amplification is observed in roscovitine- and SH-6-treated oocytes that fail to undergo nuclear envelope breakdown. Moreover, microinjection of Aurka mRNA into GV-stage oocytes cultured in 3-isobutyl-1-methyl xanthine (IBMX)-containing medium to prevent maturation also results in MOTC amplification in the absence of CDK1 activation. Overexpression of AURKA also leads to formation of an abnormal MI spindle, whereas RNAi-mediated reduction of AURKA interferes with resumption of meiosis and spindle assembly. Results of these experiments indicate that AURKA is a critical MTOC-associated component involved in resumption of meiosis, MTOC multiplication, proper spindle formation and the metaphase I-metaphase II transition.

• MeSH
• aparát dělícího vřeténka metabolismus   MeSH
• Aurora kinasa A MeSH
• blastodisk metabolismus   MeSH
• buněčný cyklus genetika   fyziologie   MeSH
• buňky NIH 3T3 MeSH
• cyklin-dependentní kinasy metabolismus   fyziologie   MeSH
• fosfatidylinositol-3-kinasy metabolismus   fyziologie   MeSH
• HeLa buňky MeSH
• kinasy Aurora MeSH
• lidé MeSH
• meióza genetika   fyziologie   MeSH
• myši inbrední BALB C MeSH
• myši inbrední C57BL MeSH
• myši MeSH
• oocyty enzymologie   fyziologie   MeSH
• organizační centrum mikrotubulů metabolismus   MeSH
• protein-serin-threoninkinasy genetika   metabolismus   fyziologie   MeSH
• protoonkogenní proteiny c-akt metabolismus   fyziologie   MeSH
• vazba proteinů 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
• AURKA protein, human MeSH Prohlížeč
• Aurka protein, mouse MeSH Prohlížeč
• Aurora kinasa A MeSH
• cyklin-dependentní kinasy MeSH
• kinasy Aurora MeSH
• protein-serin-threoninkinasy MeSH
• protoonkogenní proteiny c-akt MeSH

CDK1 is a pivotal regulator of resumption of meiosis and meiotic maturation of oocytes. CDC25A/B/C are dual-specificity phosphatases and activate cyclin-dependent kinases (CDKs). Although CDC25C is not essential for either mitotic or meiotic cell cycle regulation, CDC25B is essential for CDK1 activation during resumption of meiosis. Cdc25a -/- mice are embryonic lethal and therefore a role for CDC25A in meiosis is unknown. We report that activation of CDK1 results in a maturation-associated decrease in the amount of CDC25A protein, but not Cdc25a mRNA, such that little CDC25A is present by metaphase I. In addition, expression of exogenous CDC25A overcomes cAMP-mediated maintenance of meiotic arrest. Microinjection of Gfp-Cdc25a and Gpf-Cdc25b mRNAs constructs reveals that CDC25A is exclusively localized to the nucleus prior to nuclear envelope breakdown (NEBD). In contrast, CDC25B localizes to cytoplasm in GV-intact oocytes and translocates to the nucleus shortly before NEBD. Over-expressing GFP-CDC25A, which compensates for the normal maturation-associated decrease in CDC25A, blocks meiotic maturation at MI. This MI block is characterized by defects in chromosome congression and spindle formation and a transient reduction in both CDK1 and MAPK activities. Lastly, RNAi-mediated reduction of CDC25A results in fewer oocytes resuming meiosis and reaching MII. These data demonstrate that CDC25A behaves differently during female meiosis than during mitosis, and moreover, that CDC25A has a function in resumption of meiosis, MI spindle formation and the MI-MII transition. Thus, both CDC25A and CDC25B are critical for meiotic maturation of oocytes.

• MeSH
• AMP cyklický metabolismus   MeSH
• exprese genu MeSH
• fosfatasy cdc25 analýza   metabolismus   MeSH
• meióza * MeSH
• myši MeSH
• oocyty chemie   cytologie   enzymologie   MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH
• Názvy látek
• AMP cyklický MeSH
• Cdc25a protein, mouse MeSH Prohlížeč
• Cdc25b protein, mouse MeSH Prohlížeč
• fosfatasy cdc25 MeSH