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J Cell Sci. 2017 May 15;130(10):1760-1771. doi: 10.1242/jcs.201608. Epub 2017 Apr 12.

The PP2AB56 phosphatase promotes the association of Cdc20 with APC/C in mitosis.

Author information

1
Cell Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
2
Cell Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA foleye1@mskcc.org.

Abstract

PP2A comprising B56 regulatory subunit isoforms (PP2AB56) is a serine/threonine phosphatase essential for mitosis. At the kinetochore, PP2AB56 both stabilizes microtubule binding and promotes silencing of the spindle assembly checkpoint (SAC) through its association with the SAC protein BubR1. Cells depleted of the B56 regulatory subunits of PP2A are delayed in activation of Cdc20-containing APC/C (APC/CCdc20), which is an essential step for mitotic exit. It has been hypothesized that this delay arises from increased production of the mitotic checkpoint complex (MCC), an APC/CCdc20 inhibitor formed at unattached kinetochores through SAC signaling. In contrast to this prediction, we show that depletion of B56 subunits does not increase the amount or stability of the MCC. Rather, delays in APC/CCdc20 activation in B56-depleted cells correlate with impaired Cdc20 binding to APC/C. Stimulation of APC/CCdc20 assembly does not require binding between PP2AB56 and BubR1, and thus this contribution of PP2AB56 towards mitotic exit is distinct from its functions at kinetochores. PP2AB56 associates with APC/C constitutively in a BubR1-independent manner. A mitotic phosphorylation site on Cdc20, known to be a substrate of PP2AB56, modulates APC/CCdc20 assembly. These results elucidate the contributions of PP2AB56 towards completion of mitosis.

KEYWORDS:

APC/C; B56; Cdc20; Mitosis; PP2A

PMID:
28404789
PMCID:
PMC5450194
DOI:
10.1242/jcs.201608
[Indexed for MEDLINE]
Free PMC Article

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