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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.
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Yoon SJ, et al reported the identification of differential gene expression in germinal vesicle vs. metaphase II mouse oocytes by using annealing control primers.
By using a new innovative technology, annealing control primer-polymerase chain reaction (ACP-PCR), we identified genes that are differentially expressed in immature GV vs. in mature MII mouse oocytes. The results of the present study will be valuable in understanding the components of oocyte maturation and provide a basis for studies of human oocyte maturation.
Among the DEGs, we recognized three genes (Pscd2, PKD2, and CSN3) that have been reported to function in the protein kinase D (PKD containing pleckstrin homology domain)?COP9 signalosome (CSN) signaling pathway (9 and 10). The differential expression of these three genes in GV and MII oocytes was confirmed by quantitative real-time PCR analysis (Fig. 1C).
PKD2, a novel phorbol ester- and growth factor-stimulated protein kinase, is widely expressed in human and murine tissues and is most highly related to human PKCμ (69% identity). It contains a pleckstrin homology domain located between the duplex zinc-fingerlike motif, and a catalytic domain exhibiting all the characteristic sequence motifs of serine protein kinases (9). It has been reported that PKD is associated with the CSN, and the binding of PKD to the CSN seems to be mediated by CSN subunit 3 (CSN3) (10). The CSN is a multimeric complex that is conserved from yeast to man and is involved in regulating the stability of proteins such as p27, c-Jun, p53, and HY5, which are substrates of the Ub/26S proteasome system (12, 13, 14, 15, 16 and 17). Recently, it has been reported that disruption of CSN subunit 2 (CSN2) in mice caused deficient cell proliferation and early embryonic death (18). In Csn3−/− mice, CSN subunit 8 was not detected, suggesting that CSN3 is important for maintaining the integrity of the CSN, which itself is essential to maintain the survival of epiblast cells and thus the development of the postimplantation embryo in mice (19). Therefore, further studies as to the role of CSN3 and PKD2 in oocyte maturation are required.
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