JCB logo
R&D Systems: New Poster Available
  Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents
Published online 2 April 2001. doi:10.1083/jcb.153.1.137
This Article
Right arrow Full Text
Right arrow Full Text (PDF, 623K)
Right arrow PPT slides of all figures
Right arrow Supplemental Material Index
Right arrow Alert me when this article is cited
Right arrow Citation Map
Services
Right arrow Email this article
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new content in the JCB
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via CrossRef
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Geley, S.
Right arrow Articles by Hunt, T.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Geley, S.
Right arrow Articles by Hunt, T.
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Facebook   Add to Reddit   Add to Technorati   Add to Twitter  
What's this?

© The Rockefeller University Press, 0021-9525/2001//137 $5.00
The Journal of Cell Biology, Volume 153, Number 1, , 2001 137-148

Original Article

Anaphase-Promoting Complex/Cyclosome–Dependent Proteolysis of Human Cyclin a Starts at the Beginning of Mitosis and Is Not Subject to the Spindle Assembly Checkpoint



Stephan Geleya, Edgar Kramerb, Christian Gieffersb, Julian Gannona, Jan-Michael Petersb, and Tim Hunta

a Imperial Cancer Research Fund Clare Hall Laboratories, South Mimms, Herts EN6 3LD, United Kingdom
b Institute for Molecular Pathology, A-1030 Vienna, Austria
ICRF Clare Hall Labs, South Mimms, Potters Bar, Herts EN6 3LD, UK.44-20-7269-380444-20-7269-3981

tim.hunt{at}icrf.icnet.uk

Cyclin A is a stable protein in S and G2 phases, but is destabilized when cells enter mitosis and is almost completely degraded before the metaphase to anaphase transition. Microinjection of antibodies against subunits of the anaphase-promoting complex/cyclosome (APC/C) or against human Cdc20 (fizzy) arrested cells at metaphase and stabilized both cyclins A and B1. Cyclin A was efficiently polyubiquitylated by Cdc20 or Cdh1-activated APC/C in vitro, but in contrast to cyclin B1, the proteolysis of cyclin A was not delayed by the spindle assembly checkpoint. The degradation of cyclin B1 was accelerated by inhibition of the spindle assembly checkpoint. These data suggest that the APC/C is activated as cells enter mitosis and immediately targets cyclin A for degradation, whereas the spindle assembly checkpoint delays the degradation of cyclin B1 until the metaphase to anaphase transition. The "destruction box" (D-box) of cyclin A is 10–20 residues longer than that of cyclin B. Overexpression of wild-type cyclin A delayed the metaphase to anaphase transition, whereas expression of cyclin A mutants lacking a D-box arrested cells in anaphase.

Key Words: cyclin A • ubiquitin • APC/C • spindle assembly checkpoint • mitosis

© 2001 The Rockefeller University Press

The online version of this article contains supplemental material.

Abbreviations used in this paper: APC/C, anaphase-promoting complex/cyclosome; CFP, cyan fluorescent protein; CHX, cycloheximide; D-box, destruction box; GFP, green fluorescent protein; NEBD, nuclear envelope breakdown; SCF, Skp1/Cullin/F-box protein complex; YFP, yellow fluorescent protein.


Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Facebook Facebook   Add to Reddit Reddit   Add to Technorati Technorati   Add to Twitter Twitter    What's this?




  Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents