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Comment |
Function of COP9 Signalosome in Regulation of Mouse Oocytes Meiosis by Regulating MPF Activity and Securing Degradation. Kim E et al. The COP9 (constitutive photomorphogenic) signalosome (CSN), composed of eight subunits, is a highly conserved protein complex that regulates processes such as cell cycle progression and kinase signalling. Previously, we found the expression of the COP9 constitutive photomorphogenic homolog subunit 3 (CSN3) and subunit 5 (CSN5) changes as oocytes mature for the first time, and there is no report regarding roles of COP9 in the mammalian oocytes. Therefore, in the present study, we examined the effects of RNA interference (RNAi)-mediated transient knockdown of each subunit on the meiotic cell cycle in mice oocytes. Following knockdown of either CSN3 or CSN5, oocytes failed to complete meiosis I. These arrested oocytes exhibited a disrupted meiotic spindle and misarranged chromosomes. Moreover, down-regulation of each subunit disrupted the activity of maturation-promoting factor (MPF) and concurrently reduced degradation of the anaphase-promoting complex/cyclosome (APC/C) substrates Cyclin B1 and Securin. Our data suggest that the CSN3 and CSN5 are involved in oocyte meiosis by regulating degradation of Cyclin B1 and Securin via APC/C. Doronkin S, et al 2002 reported that CSN5/Jab1 mutations affect axis formation in the Drosophila oocyte by activating a meiotic checkpoint.
The COP9 signalosome (CSN) is linked to signaling pathways and
ubiquitin-dependent protein degradation in yeast, plant and mammalian cells,
but its roles in Drosophila development are just beginning to be understood.
The authors show that during oogenesis CSN5/JAB1, one subunit of the CSN, is required
for meiotic progression and for establishment of both the AP and DV axes of
the Drosophila oocyte. The EGFR ligand Gurken is essential for both axes, and
CSN5 mutations block the accumulation of Gurken protein
in the oocyte. CSN5 mutations also cause the modification of Vasa, which is
known to be required for Gurken translation. This CSN5 phenotype - defective
axis formation, reduced Gurken accumulation and modification of Vasa - is very
similar to the phenotype of the spindle-class genes that are required for the
repair of meiotic recombination-induced, DNA double-strand breaks. When these
breaks are not repaired, a DNA damage checkpoint mediated by mei-41 is
activated. Accordingly, the CSN5 phenotype is suppressed by mutations in
mei-41 or by mutations in mei-W68, which is required for double strand break
formation. These results suggest that, like the spindle-class genes, CSN5
regulates axis formation by checkpoint-dependent, translational control of
Gurken. They also reveal a link between DNA repair, axis formation and the
COP9 signalosome, a protein complex that acts in multiple signaling pathways
by regulating protein stability.
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