Kazuyuki Fujimitsu

Research Field

Phosphorylation cues exit from mitosis The entry and exit from the cell cycle are controlled by waves of protein phosphorylation and degradation events. Fujimitsu et al. describe the precise mechanism by which the cell cycle machinery controls exit from mitosis. The critical event is activation of a ubiquitin ligase, the anaphase-promoting complex or cyclosome (APC/C). The authors used purified components and the Xenopus egg extract system to show that two subunits of APC/C were directly phosphorylated by cyclin-dependent kinase 1 (CDK1). Phosphorylation of one subunit helped recruit CDK1 for further phosphorylation of another subunit. The second subunit interacted with the APC/C activator and target of anticancer therapy known as Cdc20. Science , this issue p. 1121

CDC20

Anaphase-promoting complex

Cyclin B1

Cyclin B

Cyclin A

10.1126/science.aad3925

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Citations (117)

PP2A‐B56 binds to Apc1 and promotes Cdc20 association with the APC/C ubiquitin ligase in mitosis

EMBO Reports (2019)

Kazuyuki Fujimitsu Hiroyuki Yamano

Abstract Cell cycle progression and genome stability are regulated by a ubiquitin ligase, the anaphase‐promoting complex/cyclosome (APC/C). Cyclin‐dependent kinase 1 (Cdk1) has long been implicated in APC/C activation; however, the molecular mechanisms of governing this process in vivo are largely unknown. Recently, a Cdk1‐dependent phosphorylation relay within Apc3‐Apc1 subunits has been shown to alleviate Apc1‐mediated auto‐inhibition by which a mitotic APC/C co‐activator Cdc20 binds to and activates the APC/C. However, the underlying mechanism for dephosphorylation of Cdc20 and APC/C remains elusive. Here, we show that a disordered loop domain of Apc1 (Apc1‐loop 500 ) directly binds the B56 regulatory subunit of protein phosphatase 2A (PP2A) and stimulates Cdc20 loading to the APC/C. Using the APC/C reconstitution system in Xenopus egg extracts, we demonstrate that mutations in Apc1‐loop 500 that abolish B56 binding decrease Cdc20 loading and APC/C‐dependent ubiquitylation. Conversely, a non‐phosphorylatable mutant Cdc20 can efficiently bind the APC/C even when PP2A‐B56 binding is impeded. Furthermore, PP2A‐B56 preferentially dephosphorylates Cdc20 over the Apc1 inhibitory domain. These results indicate that Apc1‐loop 500 plays a role in dephosphorylating Cdc20, promoting APC/C‐Cdc20 complex formation in mitosis.

CDC20

Anaphase-promoting complex

Mitotic exit

10.15252/embr.201948503

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Citations (24)

Faculty Opinions recommendation of Cyclin-Specific Docking Mechanisms Reveal the Complexity of M-CDK Function in the Cell Cycle.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature (2019)

Hiroyuki Yamano Kazuyuki Fujimitsu

Docking (animal)

10.3410/f.735781162.793563354

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