Figure 7. Models for the Dynamic Regulation of Emi2 Stability and Activity during Meta-II Arrest and for the Maintenance of Meta-II Arrest (A) Cdk1 first phosphorylates Emi2 on N-terminal Cdk1 sites (S43$T267), to the partially overlapping sites of which Cdk1, Plk1, and CK1d/ε bind. Plk1 then phosphorylates T170/195 of Emi2 to create its own (PB-dependent) stronger rebinding sites, thereby further phosphorylating the SCFb-TrCP-recognizing DSG/DSA motifs to destabilize Emi2. On the other hand, Cdk1 phosphorylates C-terminal T545/551 and S641 of the RL tail, the latter phosphorylation enabling phosphorylation of S644 by CK1d/ε; these phosphorylations prevent Emi2 from binding and inhibiting the APC/C. Upon S335/T336 phosphorylation by Rsk, however, Emi2 recruits PP2A-B56b/ε, which continuously antagonize the inhibitory phosphorylations by Cdk1/Plk1/CK1, particularly at the RL tail (and T545/551), thereby keeping upregulating Emi2 activity and stability. In the figure, the blue and red lines show the inactivation and activation pathways of Emi2, respectively. (B) Meta-II arrest is robustly maintained by both PP2A-B56b/ε activity and inhibition of PP2A-B55d. For details, see text.
Image published in: Isoda M et al. (2011)
Copyright © 2011. Image reproduced with permission of the Publisher, Elsevier B. V.
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