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PMID: 11742988 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

APC/C-mediated destruction of the centrosomal kinase Nek2A occurs in early mitosis and depends upon a cyclin A-type D-box.

The EMBO journal ·Vol. 20 ·No. 24 ·2001-12-17 ·Pages 7117-27

Hames RS, Wattam SL, Yamano H, Bacchieri R, Fry AM

Abstract

Nek2 is a NIMA-related kinase implicated in regulating centrosome structure at the G(2)/M transition. Two splice variants have been identified that exhibit distinct patterns of expression during cell cycle progression and development. Here we show that Nek2A, but not Nek2B, is destroyed upon entry into mitosis coincident with cyclin A destruction and in the presence of an active spindle assembly checkpoint. Destruction of Nek2A is mediated by the proteasome and is dependent upon the APC/C-Cdc20 ubiquitin ligase. Nek2 activity is not required for APC/C activation. Nek2A destruction in early mitosis is regulated by a motif in its extreme C-terminus which bears a striking resemblance to the extended destruction box (D-box) of cyclin A. Complete stabilization of Nek2A requires deletion of this motif and mutation of a KEN-box. Destruction of Nek2A is not inhibited by the cyclin B-type D-box, but the C-terminal domain of Nek2A inhibits destruction of both cyclins A and B. We propose that recognition of substrates by the APC/C-Cdc20 in early mitosis depends upon possession of an extended D-box motif.

MeSH Terms
Amino Acid Sequence Cyclin A/metabolism Cysteine Endopeptidases/metabolism Humans Ligases/metabolism Mitosis Molecular Sequence Data Multienzyme Complexes/metabolism NIMA-Related Kinases Proteasome Endopeptidase Complex Protein Serine-Threonine Kinases/chemistry,metabolism Sequence Homology, Amino Acid Substrate Specificity Tumor Cells, Cultured Ubiquitin/metabolism
Chemicals
Cyclin A Multienzyme Complexes Ubiquitin NEK2 protein, human NIMA-Related Kinases Protein Serine-Threonine Kinases Cysteine Endopeptidases Proteasome Endopeptidase Complex Ligases
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Hames R S
Department of Biochemistry, University of Leicester, Leicester LE1 7RH, UK.
Wattam S L
Yamano H
Bacchieri R
Fry A M
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Article Info
Journal
The EMBO journal
Abbr.
EMBO J
ISSN
0261-4189
DOI
10.1093/emboj/20.24.7117
Published
2001-12-17
Pages
7117-27
Language
English
Region
England
NLM ID
8208664
PMCID
PMC125337
Subset
IM
External Links
PubMed source DOI: 10.1093/emboj/20.24.7117 PMC Full Text View journal details
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