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Spatial regulation of APCCdh1-induced cyclin B1 degradation maintains G2 arrest in mouse oocytes

Spatial regulation of APCCdh1-induced cyclin B1 degradation maintains G2 arrest in mouse oocytes
Spatial regulation of APCCdh1-induced cyclin B1 degradation maintains G2 arrest in mouse oocytes
Within the mammalian ovary, oocytes remain arrested at G2 for several years. Then a peri-ovulatory hormonal cue triggers meiotic resumption by releasing an inhibitory phosphorylation on the kinase Cdk1. G2 arrest, however, also requires control in the concentrations of the Cdk1-binding partner cyclin B1, a process achieved by anaphase-promoting complex (APC(Cdh1)) activity, which ubiquitylates and so targets cyclin B1 for degradation. Thus, APC(Cdh1) activity prevents precocious meiotic entry by promoting cyclin B1 degradation. However, it remains unresolved how cyclin B1 levels are suppressed sufficiently to maintain arrest but not so low that they make oocytes hormonally insensitive. Here, we examined spatial control of this process by determining the intracellular location of the proteins involved and using nuclear-targeted cyclin B1. We found that raising nuclear cyclin B1 concentrations, an event normally observed in the minutes before nuclear envelope breakdown, was a very effective method of inducing the G2/M transition. Oocytes expressed only the alpha-isoform of Cdh1, which was predominantly nuclear, as were Cdc27 and Psmd11, core components of the APC and the 26S proteasome, respectively. Furthermore, APC(Cdh1) activity appeared higher in the nucleus, as nuclear-targeted cyclin B1 was degraded at twice the rate of wild-type cyclin B1. We propose a simple spatial model of G2 arrest in which nuclear APC(Cdh1)-proteasomal activity guards against any cyclin B1 accumulation mediated by nuclear import.
meiosis, mouse, oocyte, Cdh1, Fzr1, anaphase-promoting complex, cyclin B1
1477-9129
1297-1304
Holt, JE
c2b8b241-75af-4c44-972b-af9508fcfc2a
Weaver, J
4ba2b845-0a8d-4c17-bfad-0fb31ac28fe1
Jones, KT
73e8e2b5-cd67-4691-b1a9-4e7bc9066af4
Holt, JE
c2b8b241-75af-4c44-972b-af9508fcfc2a
Weaver, J
4ba2b845-0a8d-4c17-bfad-0fb31ac28fe1
Jones, KT
73e8e2b5-cd67-4691-b1a9-4e7bc9066af4

Holt, JE, Weaver, J and Jones, KT (2010) Spatial regulation of APCCdh1-induced cyclin B1 degradation maintains G2 arrest in mouse oocytes. Development, 137 (8), 1297-1304. (doi:10.1242/dev.047555). (PMID:20223764)

Record type: Article

Abstract

Within the mammalian ovary, oocytes remain arrested at G2 for several years. Then a peri-ovulatory hormonal cue triggers meiotic resumption by releasing an inhibitory phosphorylation on the kinase Cdk1. G2 arrest, however, also requires control in the concentrations of the Cdk1-binding partner cyclin B1, a process achieved by anaphase-promoting complex (APC(Cdh1)) activity, which ubiquitylates and so targets cyclin B1 for degradation. Thus, APC(Cdh1) activity prevents precocious meiotic entry by promoting cyclin B1 degradation. However, it remains unresolved how cyclin B1 levels are suppressed sufficiently to maintain arrest but not so low that they make oocytes hormonally insensitive. Here, we examined spatial control of this process by determining the intracellular location of the proteins involved and using nuclear-targeted cyclin B1. We found that raising nuclear cyclin B1 concentrations, an event normally observed in the minutes before nuclear envelope breakdown, was a very effective method of inducing the G2/M transition. Oocytes expressed only the alpha-isoform of Cdh1, which was predominantly nuclear, as were Cdc27 and Psmd11, core components of the APC and the 26S proteasome, respectively. Furthermore, APC(Cdh1) activity appeared higher in the nucleus, as nuclear-targeted cyclin B1 was degraded at twice the rate of wild-type cyclin B1. We propose a simple spatial model of G2 arrest in which nuclear APC(Cdh1)-proteasomal activity guards against any cyclin B1 accumulation mediated by nuclear import.

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More information

e-pub ahead of print date: 10 March 2010
Published date: April 2010
Keywords: meiosis, mouse, oocyte, Cdh1, Fzr1, anaphase-promoting complex, cyclin B1
Organisations: Centre for Biological Sciences

Identifiers

Local EPrints ID: 340338
URI: http://eprints.soton.ac.uk/id/eprint/340338
ISSN: 1477-9129
PURE UUID: 28423233-4148-4075-9656-bb2317fbd33d
ORCID for KT Jones: ORCID iD orcid.org/0000-0002-0294-0851

Catalogue record

Date deposited: 19 Jun 2012 13:13
Last modified: 03 Dec 2019 01:37

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