Cyclin B
is expressed predominantly in the G2/M phase of cell division. The gene product complexes with p34(cdc2) to form the
mitosis promoting factor (MPF).
NCBI Summary:
The protein encoded by this gene is a regulatory protein involved in mitosis. The gene product complexes with p34(cdc2) to form the maturation-promoting factor (MPF). The encoded protein is necessary for proper control of the G2/M transition phase of the cell cycle. [provided by RefSeq, Aug 2017]
General function
Cell death/survival, Cell cycle regulation
Comment
Cyclin B1 turnover and the mechanism causing insensitivity of fully grown mouse oocytes to cycloheximide inhibition of meiotic resumption. Han D et al. Cyclin B1 turnover and the insensitivity of fully-grown mouse oocytes to cycloheximide (CHX) inhibition of germinal vesicle breakdown (GVBD) were examined by assaying GVBD and cyclin B1 levels after treatment of oocytes with various combinations of eCG and CHX. Whereas over 95% of oocytes underwent GVBD after culture for 24 h with CHX alone, only 10% did so after culture with CHX + eCG (P < 0.05). In addition, preculture with eCG alone had no effect, but preculture with eCG + CHX prevented GVBD during a second culture with CHX alone. Therefore, we inferred that eCG delayed GVBD long enough for CHX inhibition of protein synthesis to allow cyclin B1 to decrease below a threshold where GVBD became dependent upon its de novo synthesis. However, western blot revealed no cyclin B1 synthesis, but cyclin B1 degradation, as long as GVs were maintained intact with eCG. Regarding the function of CHX in preculture without protein synthesis to block subsequent GVBD, whereas eCG delayed GVBD for only 3 h, CHX had an ongoing effect that further postponed GVBD, thus allowing cyclin B1 to decrease below the threshold. When oocytes precultured with eCG + CHX were further cultured without eCG and CHX, cyclin B1 first decreased but then, because of the ongoing effects of CHX, increased to a level sufficient to induce GVBD. The content of P34Cdc2 was not altered under any of the culture conditions (P > 0.05). We concluded that insensitivity of mouse germinal vesicle (GV) oocytes to CHX was due to the presence of sufficient cyclin B1, and that cyclin B1 level in such oocytes was maintained by an equilibrium between synthesis and degradation.
Casas E, et al 1999 reported changes in cyclin B localisation during pig oocyte in vitro
maturation.
The localisation of cyclin B throughout in vitro maturation of pig oocytes was
determined by indirect immunofluorescence using a monoclonal antibody specific
for an epitope of the human cyclin B. Maturation of pig oocytes was induced by
addition of Pergonal (2 UI/ml of FSH/LH) and beta-oestradiol to the medium
where isolated ovarian follicles were cultured for up to 72 h.
Immature
oocytes showed cyclin B immunofluorescent staining in the cytoplasm, whereas
mature oocytes showed the immunofluorescent label concentrated in the nucleus.
Metaphase chromosomes showed an intense immunofluorescence. The migration
of cyclin B to the nucleus and its association with metaphase chromosomes in pig
oocytes able to progress through meiosis resembled the subcellular localisation of
cyclin B and the distribution of maturation promoting factor (MPF) in mitotic
dividing cells.Josefsberg LBY, et al reported that the proteasome is involved in the first metaphase-to-anaphase
transition of meiosis in rat oocytes
Among other cellular professes, the proteasome
participates in degradation of ubiquinated cyclins in mitosis. Inactivation of the mitosis promoting factor (MPF), occurring between the two
meiotic divisions, is associated with degradation of cyclin B. They found that
upon resumption of meiosis, proteasomes translocate to the spindle apparatus.
It was demonstrated that specific inhibitors of proteasome catalytic
activity, MG132 and lactacystin, blocked polar body extrusion. Chromosome and
microtubule fluorescent staining verified that MG132-treated oocytes were
arrested at metaphase I. Intervention of proteasomal action with this
inhibitor also resulted in accumulation of cyclin B and elevated activity of
MPF.
Allegro: Analyzing expression and sequence in concert to discover regulatory programs. Halperin Y et al. A major goal of system biology is the characterization of transcription factors and microRNAs (miRNAs) and the transcriptional programs they regulate. We present Allegro, a method for de-novo discovery of cis-regulatory transcriptional programs through joint analysis of genome-wide expression data and promoter or 3' UTR sequences. The algorithm uses a novel log-likelihood-based, non-parametric model to describe the expression pattern shared by a group of co-regulated genes. We show that Allegro is more accurate and sensitive than existing techniques, and can simultaneously analyze multiple expression datasets with more than 100 conditions. We apply Allegro on datasets from several species and report on the transcriptional modules it uncovers. Our analysis reveals a novel motif over-represented in the promoters of genes highly expressed in murine oocytes. The present gene id highly expressed in the oocyte and has a unique promoter motif.
Two B-type cyclins, B1 and B2 , have been identified in mammals. Proliferating cells express both cyclins,
which bind to and activate p34 (CDC2).
Differential regulation of cyclin B1 degradation between the first and second meiotic divisions of bovine oocytes. Liu W et al. During mammalian oocyte maturation, two consecutive meiotic divisions are required to form a haploid gamete. For each meiotic division, oocytes must transfer from metaphase to anaphase, but maturation promoting factor (cyclin-dependent kinase 1/cyclin B1) activity would keep the oocytes at metaphase. Therefore, inactivation of maturation promoting factor is needed to finish the transition and complete both these divisions; this is provided through anaphase-promoting complex/cyclosome-dependent degradation of cyclin B1. The objective of this study was to examine meiotic divisions in bovine oocytes after expression of a full length cyclin B1 and a nondegradable N-terminal 87 amino acid deletion, coupled with the fluorochrome Venus, by microinjecting their complementary RNA (cRNA). Overexpression of full-length cyclin B1-Venus inhibited homologue disjunction and first polar body formation in maturing oocytes (control 70% vs. overexpression 16%; P < 0.05). However at the same levels of expression, it did not block second meiotic metaphase and cleavage of eggs after parthenogenetic activation (control: 82% pronuclei and 79% cleaved; overexpression: 91% pronuclei and 89% cleaved). The full length cyclin B1 and a nondegradable N-terminal 87 amino acid deletion caused metaphase arrest in both meiotic divisions, whereas degradation of securin was unaffected. Roscovitine, a potent cyclin-dependent kinase 1 (CDK1) inhibitor, overcame this metaphase arrest in maturing oocytes at 140 ?M, but higher doses (200 ?M) were needed to overcome arrest in eggs. In conclusion, because metaphase I (MI) blocked by nondegradable cyclin B1 was distinct from metaphase II (MII) in their different sensitivities to trigger CDK1 inactivation, we concluded that mechanisms of MI arrest differed from MII arrest.
Follicle stages
Primordial, Primary, Secondary, Antral, Preovulatory, Corpus luteum
Comment
Expression of Cyclin B1 Messenger RNA Isoforms and Initiation of Cytoplasmic Polyadenylation in the Bovine Oocyte Tremblay K, et al .
Oocytes can synthesize and store maternal mRNA in an inactive translational state until the start of in vitro maturation. Cytoplasmic polyadenylation, driven by 3' UTR cis-acting cytoplasmic polyadenylation element (CPE), is associated with translational activation of cyclin B1 mRNA during maturation. The main aim of this study was to investigate if bovine oocyte cyclin B1 mRNA undergoes cytoplasmic polyadenylation/translation during in vitro maturation, like in other species. We have found that cyclin B1 mRNA is present in two isoforms, consisting of the same open reading frame but with different 3' UTR lengths. Only the longest isoform (cyclin B1L) has a putative CPE sequence and other regulatory sequences and its mRNA level decreases during early embryo development. The polyadenylation state of cyclin B1L during in vitro maturation was studied. Results demonstrated that cyclin B1L bears a relatively long poly(A) tail in GV stage oocytes which is further lengthened at 10 h of maturation, before metaphase I. Interestingly, cyclin B1L bears a short poly(A) tail when the ovaries and the oocytes are transported and manipulated on ice to stop the polyadenylation process. Cytoplasmic polyadenylation occurs most probably during ovary transport in warm saline when oocytes are still in their follicular environment. Our results also show a link between cytoplasmic polyadenylation of cyclin B1 and translation/appearance of cyclin B1 protein before in vitro maturation.
Phenotypes
Mutations
2 mutations
Species: mouse
Mutation name: None
type: null mutation fertility: embryonic lethal Comment: To test whether the 2 B-type cyclins have distinct roles, Brandeis et al. (1998)
generated lines of transgenic mice, one lacking cyclin B1 and the other lacking B2. Cyclin B1 proved to be an essential
gene; no homozygous B1-null pups were born. In contrast, nullizygous B2 mice developed normally and did not display
any obvious abnormalities.
Species: mouse
Mutation name: type: null mutation fertility: infertile - ovarian defect Comment: Cyclin B2 can compensate for Cyclin B1 in oocyte meiosis I. Li J et al. (2018) Mammalian oocytes are arrested at the prophase of the first meiotic division for months and even years, depending on species. Meiotic resumption of fully grown oocytes requires activation of M-phase-promoting factor (MPF), which is composed of Cyclin B1 and cyclin-dependent kinase 1 (CDK1). It has long been believed that Cyclin B1 synthesis/accumulation and its interaction with CDK1 is a prerequisite for MPF activation in oocytes. In this study, we revealed that oocyte meiotic resumption occurred in the absence of Cyclin B1. Ccnb1-null oocytes resumed meiosis and extruded the first polar body. Without Cyclin B1, CDK1 could be activated by up-regulated Cyclin B2. Ccnb1 and Ccnb2 double knockout permanently arrested the oocytes at the prophase of the first meiotic division. Oocyte-specific Ccnb1-null female mice were infertile due to failed MPF activity elevation and thus premature interphase-like stage entry in the second meiotic division. These results have revealed a hidden compensatory mechanism between Cyclin B1 and Cyclin B2 in regulating MPF and oocyte meiotic resumption.//////////////////