Abstract
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.
Highlights
The COP9 signalosome (CSN) was first identified in Arabidopsis thaliana as a repressor of photomorphogenesis and is conserved evolutionally from yeast to human [1,2]
Our results demonstrate that constitutive photomorphogenic homolog subunit 3 (CSN3) or CSN5 knockdown leads to meiosis I arrest, disruption of maturation promoting factor (MPF) activity, and decreased degradation of anaphase-promoting complex/cyclosome (APC/C) substrates
The CSN is a multimeric complex consisting of eight subunits (CSN1 to CSN8) that share significant sequence homology with the eight subunits of the 26S proteasome lid complex [31]
Summary
The COP9 signalosome (CSN) was first identified in Arabidopsis thaliana as a repressor of photomorphogenesis and is conserved evolutionally from yeast to human [1,2]. The CSN interacts with several kinases [4,5,6], recruits deubiquitination enzymes, and has an intrinsic isopeptidase activity for deneddylation [7,8] With these activities, the CSN is involved in regulating various processes including invertebrate development [9], cell cycle [10,11,12], kinase signaling [13], and nuclear transport [14]. Some reports indicate an essential role of the CSN in mammalian early embryonic development and cell cycle regulation, the function of CSN subunits in mammalian oocyte meiotic maturation remains poorly understood
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