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

Content Provider	PubMed Central
Author	Hames, Rebecca S. Wattam, Samantha L. Yamano, Hiroyuki Rachid, Bacchieri Fry, Andrew M.
Copyright Year	2001
Abstract	Nek2 is a NIMA-related kinase implicated in regulating centrosome structure at the G2/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.
Related Links	http://dx.doi.org/10.1093/emboj/20.24.7117
Ending Page	7127
Page Count	11
Starting Page	7117
File Format	PDF
ISSN	14602075
e-ISSN	14602075
Journal	The EMBO Journal
Issue Number	24
Volume Number	20
Language	English
Publisher	Oxford University Press
Publisher Date	2001-12-17
Access Restriction	Open
Rights Holder	Oxford University Press
Subject Keyword	Biochemistry, Genetics and Molecular Biology(all) Immunology and Microbiology(all) Neuroscience(all) Molecular Biology Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Neuroscience Immunology and Microbiology Medicine Molecular Biology

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