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Emi2 inhibition of the anaphase-promoting complex/cyclosome absolutely requires Emi2 binding via the C-terminal RL tail.

Ohe M, Kawamura Y, Ueno H, Inoue D, Kanemori Y, Senoo C, Isoda M, Nakajo N, Sagata N - Mol. Biol. Cell (2010)

Bottom Line: Furthermore, and importantly, the RL tail-mediated binding apparently promotes the inhibitory interactions of the D-box and the ZBR (of Emi2) with the APC/C.Finally, Emi1, a somatic paralog of Emi2, also has a functionally similar RL tail.We propose that the RL tail of Emi1/Emi2 serves as a docking site for the APC/C, thereby promoting the interaction and inhibition of the APC/C by the D-box and the ZBR.

View Article: PubMed Central - PubMed

Affiliation: Department of Biology, Graduate School of Sciences, Kyushu University, Fukuoka 812-8581, Japan.

ABSTRACT
Emi2 (also called Erp1) inhibits the anaphase-promoting complex/cyclosome (APC/C) and thereby causes metaphase II arrest in unfertilized vertebrate eggs. Both the D-box and the zinc-binding region (ZBR) of Emi2 have been implicated in APC/C inhibition. However, it is not well known how Emi2 interacts with and hence inhibits the APC/C. Here we show that Emi2 binds the APC/C via the C-terminal tail, termed here the RL tail. When expressed in Xenopus oocytes and egg extracts, Emi2 lacking the RL tail fails to interact with and inhibit the APC/C. The RL tail itself can directly bind to the APC/C, and, when added to egg extracts, either an excess of RL tail peptides or anti-RL tail peptide antibody can dissociate endogenous Emi2 from the APC/C, thus allowing APC/C activation. Furthermore, and importantly, the RL tail-mediated binding apparently promotes the inhibitory interactions of the D-box and the ZBR (of Emi2) with the APC/C. Finally, Emi1, a somatic paralog of Emi2, also has a functionally similar RL tail. We propose that the RL tail of Emi1/Emi2 serves as a docking site for the APC/C, thereby promoting the interaction and inhibition of the APC/C by the D-box and the ZBR.

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A two-step model for the inhibition of the APC/C by Emi1/Emi2. Emi1/Emi2 inhibit the APC/C by two steps: (1) docking onto the APC/C via the RL tail, and (2) interaction and inhibition of the APC/C by the D-box and the ZBR.
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Figure 6: A two-step model for the inhibition of the APC/C by Emi1/Emi2. Emi1/Emi2 inhibit the APC/C by two steps: (1) docking onto the APC/C via the RL tail, and (2) interaction and inhibition of the APC/C by the D-box and the ZBR.

Mentions: On the basis of the results with Emi1 (and partly Emi2 itself), the (physical) interaction of Emi2 with the APC/C has been thought to be mediated primarily by the D-box and possibly also by the ZBR. In this study, however, we clearly show that the C-terminal tail, termed here the RL tail or motif, is essential for the interaction of Emi2 (as well as Emi1) with the APC/C. The RL motif seems to serve as a docking site of Emi1/Emi2 for the APC/C, thereby promoting the interactions of the D-box and the ZBR with the APC/C and hence enabling the inhibition of the APC/C (Figure 6). Our results thus provide an important mechanistic insight into how Emi1/Emi2 interact with and inhibit the APC/C. In the future, elucidation of the precise binding site(s) of the RL motif, as well as those of the D-box and the ZBR, within the APC/C will greatly contribute to our better understanding of the molecular mechanism of APC/C regulation by Emi1/Emi2.


Emi2 inhibition of the anaphase-promoting complex/cyclosome absolutely requires Emi2 binding via the C-terminal RL tail.

Ohe M, Kawamura Y, Ueno H, Inoue D, Kanemori Y, Senoo C, Isoda M, Nakajo N, Sagata N - Mol. Biol. Cell (2010)

A two-step model for the inhibition of the APC/C by Emi1/Emi2. Emi1/Emi2 inhibit the APC/C by two steps: (1) docking onto the APC/C via the RL tail, and (2) interaction and inhibition of the APC/C by the D-box and the ZBR.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2836971&req=5

Figure 6: A two-step model for the inhibition of the APC/C by Emi1/Emi2. Emi1/Emi2 inhibit the APC/C by two steps: (1) docking onto the APC/C via the RL tail, and (2) interaction and inhibition of the APC/C by the D-box and the ZBR.
Mentions: On the basis of the results with Emi1 (and partly Emi2 itself), the (physical) interaction of Emi2 with the APC/C has been thought to be mediated primarily by the D-box and possibly also by the ZBR. In this study, however, we clearly show that the C-terminal tail, termed here the RL tail or motif, is essential for the interaction of Emi2 (as well as Emi1) with the APC/C. The RL motif seems to serve as a docking site of Emi1/Emi2 for the APC/C, thereby promoting the interactions of the D-box and the ZBR with the APC/C and hence enabling the inhibition of the APC/C (Figure 6). Our results thus provide an important mechanistic insight into how Emi1/Emi2 interact with and inhibit the APC/C. In the future, elucidation of the precise binding site(s) of the RL motif, as well as those of the D-box and the ZBR, within the APC/C will greatly contribute to our better understanding of the molecular mechanism of APC/C regulation by Emi1/Emi2.

Bottom Line: Furthermore, and importantly, the RL tail-mediated binding apparently promotes the inhibitory interactions of the D-box and the ZBR (of Emi2) with the APC/C.Finally, Emi1, a somatic paralog of Emi2, also has a functionally similar RL tail.We propose that the RL tail of Emi1/Emi2 serves as a docking site for the APC/C, thereby promoting the interaction and inhibition of the APC/C by the D-box and the ZBR.

View Article: PubMed Central - PubMed

Affiliation: Department of Biology, Graduate School of Sciences, Kyushu University, Fukuoka 812-8581, Japan.

ABSTRACT
Emi2 (also called Erp1) inhibits the anaphase-promoting complex/cyclosome (APC/C) and thereby causes metaphase II arrest in unfertilized vertebrate eggs. Both the D-box and the zinc-binding region (ZBR) of Emi2 have been implicated in APC/C inhibition. However, it is not well known how Emi2 interacts with and hence inhibits the APC/C. Here we show that Emi2 binds the APC/C via the C-terminal tail, termed here the RL tail. When expressed in Xenopus oocytes and egg extracts, Emi2 lacking the RL tail fails to interact with and inhibit the APC/C. The RL tail itself can directly bind to the APC/C, and, when added to egg extracts, either an excess of RL tail peptides or anti-RL tail peptide antibody can dissociate endogenous Emi2 from the APC/C, thus allowing APC/C activation. Furthermore, and importantly, the RL tail-mediated binding apparently promotes the inhibitory interactions of the D-box and the ZBR (of Emi2) with the APC/C. Finally, Emi1, a somatic paralog of Emi2, also has a functionally similar RL tail. We propose that the RL tail of Emi1/Emi2 serves as a docking site for the APC/C, thereby promoting the interaction and inhibition of the APC/C by the D-box and the ZBR.

Show MeSH
Related in: MedlinePlus