DOI: 10.1101/gad.1007302. Identification of a new APC/C recognition domain, the A box, which is required for the Cdh1-dependent destruction of the kinase Aurora-A during mitotic exit

Identification of a new APC/C recognition domain, the A box, which is required for the Cdh1-dependent destruction of the kinase Aurora-A during mitotic exit

10.1101/gad.1007302

Crossref journal-article

Cold Spring Harbor Laboratory

Genes & Development (246)

Abstract

The mitotic kinase Aurora A (Aur-A) is required for formation of a bipolar mitotic spindle and accurate chromosome segregation. In somatic cells, Aur-A protein and kinase activity levels peak during mitosis, and Aur-A is degraded during mitotic exit. Here, we investigated how Aur-A protein and kinase activity levels are regulated, taking advantage of the rapid synchronous cell division cycles ofXenopus eggs and cell-free systems derived from them. Aur-A kinase activity oscillates in the early embryonic cell cycles, just as in somatic cells, but Aur-A protein levels are constant, indicating that regulated activation and inactivation, instead of periodic proteolysis, is the dominant mode of Aur-A regulation in these cell cycles. Cdh1, the APC/C activator that targets many mitotic proteins for ubiquitin-dependent proteolysis during late mitosis and G1 in somatic cells, is missing in Xenopus eggs and early embryos. We find that addition of Cdh1 to egg extracts undergoing M phase exit is sufficient to induce rapid degradation of Aur-A. Aur-A contains both of the two known APC/C recognition signals, (1) a C-terminal D box similar to those required for ubiquitin-dependent destruction of cyclin B and several other mitotic proteins, and (2) an N-terminal KEN box similar to that found on cdc20, which is ubiquitinated in response to APC/CCdh1. The D box is required for Cdh1-induced destruction of Aur-A but the KEN box is not. Destruction also requires a short region in the N terminus, which contains a newly identified recognition signal, the A box. The A box is conserved in vertebrate Aur-As and contains serine 53, which is phosphorylated during M phase. Mutation of serine 53 to aspartic acid, which can mimic the effect of phosphorylation, completely blocks Cdh1-dependent destruction of Aur-A. These results suggest that dephosphorylation of serine 53 during mitotic exit could control the timing of Aur-A destruction, allowing recognition of both the A box and D box by Cdh1-activated APC/C.

Bibliography

Littlepage, L. E., & Ruderman, J. V. (2002). Identification of a new APC/C recognition domain, the A box, which is required for the Cdh1-dependent destruction of the kinase Aurora-A during mitotic exit. Genes & Development, 16(17), 2274â2285.

Authors 2

Laurie E. Littlepage (first)
Joan V. Ruderman (additional)

References 58 Referenced 233

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Dates

Type	When
Created	22 years, 11 months ago (Sept. 3, 2002, 12:44 p.m.)
Deposited	3 years, 9 months ago (Nov. 15, 2021, 11:14 a.m.)
Indexed	1 month, 4 weeks ago (June 26, 2025, 2:24 p.m.)
Issued	22 years, 11 months ago (Sept. 1, 2002)
Published	22 years, 11 months ago (Sept. 1, 2002)
Published Online	22 years, 11 months ago (Sept. 1, 2002)
Published Print	22 years, 11 months ago (Sept. 1, 2002)

Funders 0

None

BibTeX

@article{Littlepage_2002, title={Identification of a new APC/C recognition domain, the A box, which is required for the Cdh1-dependent destruction of the kinase Aurora-A during mitotic exit}, volume={16}, ISSN={1549-5477}, url={http://dx.doi.org/10.1101/gad.1007302}, DOI={10.1101/gad.1007302}, number={17}, journal={Genes & Development}, publisher={Cold Spring Harbor Laboratory}, author={Littlepage, Laurie E. and Ruderman, Joan V.}, year={2002}, month=sep, pages={2274–2285} }

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