BubR1 N Terminus Acts as a Soluble Inhibitor of Cyclin B Degradation by APC/CCdc20 in Interphase

Liviu A. Malureanu, Karthik B. Jeganathan, Masakazu Hamada, Lisa Wasilewski, James Davenport, Jan Van Deursen

Research output: Contribution to journalArticle

130 Citations (Scopus)

Abstract

BubR1 is an essential mitotic checkpoint protein with multiple functional domains. It has been implicated in mitotic checkpoint control, as an active kinase at unattached kinetochores, and as a cytosolic inhibitor of APC/CCdc20 activity, as well as in mitotic timing and stable chromosome-spindle attachment. Using BubR1-conditional knockout cells and BubR1 domain mutants, we demonstrate that the N-terminal Cdc20 binding domain of BubR1 is essential for all of these functions, whereas its C-terminal Cdc20-binding domain, Bub3-binding domain, and kinase domain are not. We find that the BubR1 N terminus binds to Cdc20 in a KEN box-dependent manner to inhibit APC/C activity in interphase, thereby allowing accumulation of cyclin B in G2 phase prior to mitosis onset. Together, our results suggest that kinetochore-bound BubR1 is nonessential and that soluble BubR1 functions as a pseudosubstrate inhibitor of APC/CCdc20 during interphase to prevent unscheduled degradation of specific APC/C substrates.

Original languageEnglish (US)
Pages (from-to)118-131
Number of pages14
JournalDevelopmental Cell
Volume16
Issue number1
DOIs
StatePublished - Jan 20 2009

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M Phase Cell Cycle Checkpoints
Cyclin B
Kinetochores
Interphase
Corrosion inhibitors
Phosphotransferases
Degradation
G2 Phase
Chromosomes
Mitosis
Substrates
Proteins

Keywords

  • CELLBIO

ASJC Scopus subject areas

  • Developmental Biology

Cite this

BubR1 N Terminus Acts as a Soluble Inhibitor of Cyclin B Degradation by APC/CCdc20 in Interphase. / Malureanu, Liviu A.; Jeganathan, Karthik B.; Hamada, Masakazu; Wasilewski, Lisa; Davenport, James; Van Deursen, Jan.

In: Developmental Cell, Vol. 16, No. 1, 20.01.2009, p. 118-131.

Research output: Contribution to journalArticle

Malureanu, Liviu A. ; Jeganathan, Karthik B. ; Hamada, Masakazu ; Wasilewski, Lisa ; Davenport, James ; Van Deursen, Jan. / BubR1 N Terminus Acts as a Soluble Inhibitor of Cyclin B Degradation by APC/CCdc20 in Interphase. In: Developmental Cell. 2009 ; Vol. 16, No. 1. pp. 118-131.
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