Disease relevance of CycA

• In the central nervous system (CNS) of Drosophila embryos lacking regulator of cyclin A (rca1) or cyclin A, we observe that several ganglion mother cells (GMCs) fail to divide [1].

High impact information on CycA

• Rather, rux appears to act through cyclin A during premeiotic G2 to regulate meiosis II [2].
• We propose that cyclin A-cdc2 kinase at the G2 to M transition of meiosis I activates a target necessary for meiosis II, thereby coupling the two meiotic divisions [2].
• Indeed, in mutant embryos deficient in cyclin A, cells that accumulate only cyclin B do not enter mitosis [3].
• Expression and function of Drosophila cyclin A during embryonic cell cycle progression [4].
• Immunofluorescent staining revealed that cyclin A accumulates in the interphase cytoplasm of cellularized embryos, but relocates to the nuclear region early in prophase and is completely degraded within metaphase [4].

Biological context of CycA

• Surprisingly, nuclear accumulation was not required, and even a membrane-tethered form of CycA was able to induce mitosis [5].
• Cyclin A (CycA), the only essential mitotic cyclin in Drosophila, is cytoplasmic during interphase and accumulates in the nucleus during prophase [5].
• The essential mitotic function of CycA is therefore not the activation of numerous mitotic substrates by Cdk1-dependent phosphorylation [5].
• CycA has seven exons and six introns, and its transcription unit spans 6 kb [6].
• In roughex (rux) mutants, cells enter S phase precociously because of ectopic activation of a Cyclin A/Cdk complex in early G1 [7].

Anatomical context of CycA

• In larvae, cyclin A is expressed predominantly in brain and imaginal disks, whereas cyclin B transcripts are abundant in testes [8].
• Cyclin A is present at its highest concentrations throughout the cytoplasm during the interphase periods of the blastoderm cycles, although weak punctate staining can also be detected in the nucleus [9].
• Neural cell fate in rca1 and cycA mutants: the roles of intrinsic and extrinsic factors in asymmetric division in the Drosophila central nervous system [1].
• Cyclin A is not detectable in unfertilized eggs and is present at low levels prior to cellularization of the syncytial embryo [10].
• In cells arrested at c-metaphase by treating with microtubule destabilizing drugs to prevent spindle formation, cyclin A has been degraded in the arrested cells, whereas cyclin B is maintained at high levels [10].

Associations of CycA with chemical compounds

• This study suggests that, in fruit fly embryos, 1) there is a dose-dependent relationship between cell cycle length and O2 levels in fruit fly embryos, and 2) stabilized cyclin A and E2F1 are likely to be the mediators of hypoxia-induced arrest at metaphase and pre-S phase [11].

Regulatory relationships of CycA

• Expression of rca1 transgenes in G1 or in postmitotic neurons promotes Cyclin A protein accumulation and drives cells into S phase in a Cyclin A-dependent fashion [7].
• Surprisingly, Rux had a stimulating effect on CycA-Cdk1 activity when present in low concentrations [12].
• Taken together, our observations support the hypothesis that cyclin B regulates cytoskeletal changes while cyclin A regulates the nuclear cycles [13].
• These results demonstrate that CycA is directly regulated by PcG proteins, linking them to cell cycle control in vivo [14].
• Cut promoted Cyclin A expression by negatively regulating Fizzy-related [15].

Other interactions of CycA

• Given that Dally is known to regulate the activity of secreted growth factors our findings suggest that extracellular cues influence the degradation of Cyclin A in a manner that controls cell cycle progression and ultimately, cell division patterning [16].
• We show that both genes encode abundant maternal mRNAs, but whereas the cyclin A mRNA is relatively uniformly distributed before cell formation, the cyclin B mRNA becomes localized to the developing pole cells [8].
• While the loss of N leads to the specification of RP2 fates to both progeny of GMC-1 and loss of nb results in the specification of sib fates to these daughter cells, the GMC-1 in the double mutant between nb and cycA assumes a sib fate [17].
• We have done experiments to investigate a potential functional overlap between two kinases (Dmcdc2 and Dmcdc2c) and two cyclins (cyclin A and cyclin B) [18].
• Finally, loss of function of the Pc gene and overexpression of Pc and ph trigger up-regulation and down-regulation, respectively, of CycA expression in embryos [14].

Analytical, diagnostic and therapeutic context of CycA

• Sequence analysis of the mutant genome reveals that a P element is inserted into the first intron of the Cyclin-A gene [19].
• Consistent with the decrease in the proportion of cells in S and G2, western blots show that levels of cyclin A, which is required during the S phase of the cycle, decreased in 20E-treated cells [20].

References