Nejvíce citovaný článek - PubMed ID 21969023
Proteasomal degradation of ubiquitinated proteins in oocyte meiosis and fertilization in mammals
The degradation of maternally provided molecules is a very important process during early embryogenesis. However, the vast majority of studies deals with mRNA degradation and protein degradation is only a very little explored process yet. The aim of this article was to summarize current knowledge about the protein degradation during embryogenesis of mammals. In addition to resuming of known data concerning mammalian embryogenesis, we tried to fill the gaps in knowledge by comparison with facts known about protein degradation in early embryos of non-mammalian species. Maternal protein degradation seems to be driven by very strict rules in terms of specificity and timing. The degradation of some maternal proteins is certainly necessary for the normal course of embryonic genome activation (EGA) and several concrete proteins that need to be degraded before major EGA have been already found. Nevertheless, the most important period seems to take place even before preimplantation development-during oocyte maturation. The defects arisen during this period seems to be later irreparable.
- Klíčová slova
- Autophagy, Embryonic genome activation, Maternal to zygotic transition, Proteasome system, Ubiquitin, Ubiquitin ligase,
- MeSH
- embryo nesavčí metabolismus fyziologie MeSH
- embryo savčí metabolismus fyziologie MeSH
- embryonální vývoj fyziologie MeSH
- genom fyziologie MeSH
- lidé MeSH
- oocyty metabolismus fyziologie MeSH
- proteiny metabolismus MeSH
- vývojová regulace genové exprese fyziologie MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- Názvy látek
- proteiny MeSH
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
The degradation of maternal proteins is one of the most important events during early development, and it is presumed to be essential for embryonic genome activation (EGA), but the precise mechanism is still not known. It is thought that a large proportion of the degradation of maternal proteins is mediated by the ubiquitin-proteolytic system. In this study we focused on the expression of the Skp1-Cullin1-F-box (SCF) complex, a modular RING-type E3 ubiquitin-ligase, during bovine preimplantation development. The complex consists of three invariable components--Cul1, Skp1, Rbx1 and F-box protein, which determines the substrate specificity. The protein level and mRNA expression of all three invariable members were determined. Cul1 and Skp1 mRNA synthesis was activated at early embryonic stages, at the 4c and early 8c stage, respectively, which suggests that these transcripts are necessary for preparing the embryo for EGA. CUL1 protein level increased from MII to the morula stage, with a significant difference between MII and L8c, and between MII and the morula. The CUL1 protein was localized primarily to nuclei and to a lesser extent to the cytoplasm, with a lower signal in the inner cell mass (ICM) compared to the trophectoderm (TE) at the blastocyst stage. The level of SKP1 protein significantly increased from MII oocytes to 4c embryos, but then significantly decreased again. The localization of the SKP1 protein was analysed throughout the cell and similarly to CUL1 at the blastocyst stage, the staining was less intensive in the ICM. There were no statistical differences in RBX1 protein level and localization. The active SCF-complex, which is determined by the interaction of Cul1 and Skp1, was found throughout the whole embryo during preimplantation development, but there was a difference at the blastocyst stage, which exhibits a much stronger signal in the TE than in the ICM. These results suggest that all these genes could play an important role during preimplantation development. This paper reveals comprehensive expression profile, the basic but important knowledge necessary for further studying.
- MeSH
- blastocysta metabolismus ultrastruktura MeSH
- embryonální vývoj genetika MeSH
- F-box proteiny genetika metabolismus MeSH
- fertilizace in vitro MeSH
- genetická transkripce MeSH
- kulinové proteiny genetika metabolismus MeSH
- messenger RNA genetika metabolismus MeSH
- oocyty cytologie růst a vývoj metabolismus MeSH
- proteinligasy komplexu SCF genetika metabolismus MeSH
- proteiny asociované s kinázou S-fáze genetika metabolismus MeSH
- signální transdukce MeSH
- skot MeSH
- spermie cytologie metabolismus MeSH
- substrátová specifita MeSH
- vývojová regulace genové exprese MeSH
- zinkové prsty genetika MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- skot MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- Cullin 1 MeSH Prohlížeč
- F-box proteiny MeSH
- kulinové proteiny MeSH
- messenger RNA MeSH
- proteinligasy komplexu SCF MeSH
- proteiny asociované s kinázou S-fáze MeSH
Regulation of mRNA translation by cytoplasmic polyadenylation is known to be important for oocyte maturation and further development. This process is generally controlled by phosphorylation of cytoplasmic polyadenylation element binding protein 1 (CPEB1). The aim of this study is to determine the role of Aurora kinase A in CPEB1 phosphorylation and the consequent CPEB1-dependent polyadenylation of maternal mRNAs during mammalian oocyte meiosis. For this purpose, we specifically inhibited Aurora kinase A with MLN8237 during meiotic maturation of porcine oocytes. Using poly(A)-test PCR method, we monitored the effect of Aurora kinase A inhibition on poly(A)-tail extension of long and short cyclin B1 encoding mRNAs as markers of CPEB1-dependent cytoplasmic polyadenylation. Our results show that inhibition of Aurora kinase A activity impairs neither cyclin B1 mRNA polyadenylation nor its translation and that Aurora kinase A is unlikely to be involved in CPEB1 activating phosphorylation.
- MeSH
- Aurora kinasa A metabolismus MeSH
- cyklin B1 genetika MeSH
- faktory štěpení a polyadenylace mRNA chemie metabolismus MeSH
- fosforylace MeSH
- meióza * MeSH
- messenger RNA metabolismus MeSH
- oocyty enzymologie metabolismus MeSH
- polyadenylace MeSH
- Sus scrofa metabolismus MeSH
- zvířata MeSH
- Check Tag
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- Aurora kinasa A MeSH
- cyklin B1 MeSH
- faktory štěpení a polyadenylace mRNA MeSH
- messenger RNA MeSH