Emi1 regulates the anaphase-promoting complex by a different mechanism than Mad2 proteins

Genes and Development - Tập 15 Số 24 - Trang 3278-3285 - 2001
Julie D.R. Reimann1, Bryan Gardner2, Florence Margottin-Goguet2, Peter K. Jackson2
1Department of Pathology, Stanford University School of Medicine, Stanford, California 94305-5324, USA
2Departments of Pathology, Microbiology and Immunology, Stanford University School of Medicine, Stanford, California 94305-5324, USA

Tóm tắt

The anaphase-promoting complex/cyclosome (APC) ubiquitin ligase is activated by Cdc20 and Cdh1 and inhibited by Mad2 and the spindle assembly checkpoint complex, Mad2B, and the early mitotic inhibitor Emi1. Mad2 inhibits APCCdc20, whereas Mad2B preferentially inhibits APCCdh1. We have examined the mechanism of APC inhibition by Emi1 and find that unlike Mad2 proteins, Emi1 binds and inhibits both APCCdh1 and APCCdc20. Also unlike Mad2, Emi1 stabilizes cyclin A in the embryo and requires zinc for its APC inhibitory activity. We find that Emi1 binds the substrate-binding region of Cdc20 and prevents substrate binding to the APC, illustrating a novel mechanism of APC inhibition.

Từ khóa


Tài liệu tham khảo

10.1016/S0092-8674(01)00410-X

10.1101/gad.917901

10.1101/gad.898701

Chen, 1999, The spindle checkpoint of budding yeast depends on a tight complex between the Mad1 and Mad2 proteins., Mol. Biol. Cell, 10, 2607, 10.1091/mbc.10.8.2607

10.1002/gene.1017

10.1101/gad.10.24.3081

10.1073/pnas.250351297

10.1083/jcb.153.1.121

10.1101/gad.11.1.94

Fang, 1998, The checkpoint protein MAD2 and the mitotic regulator CDC20 form a ternary complex with the anaphase-promoting complex to control anaphase initiation., Genes & Dev., 12, 1871, 10.1101/gad.12.12.1871

10.1016/S1097-2765(00)80126-4

10.1083/jcb.153.1.137

10.1038/349132a0

10.1073/pnas.97.16.8973

10.1016/S0960-9822(01)00399-2

10.1083/jcb.116.3.707

10.1126/science.279.5353.1041

10.1016/S0092-8674(00)81148-4

10.1083/jcb.141.6.1393

10.1126/science.279.5353.1045

10.1016/S0960-9822(07)00510-6

Kramer, 2000, Mitotic regulation of the APC activator proteins CDC20 and CDH1., Mol. Biol. Cell, 11, 1555, 10.1091/mbc.11.5.1555

10.1093/emboj/17.13.3565

10.1038/44611

10.1038/73338

Murray, 1991, Cell cycle extracts., Methods Cell Biol., 36, 581, 10.1016/S0091-679X(08)60298-8

10.1146/annurev.biochem.68.1.583

Pfleger, 2000, The KEN box: An APC recognition signal distinct from the D box targeted by Cdh1., Genes & Dev., 14, 655, 10.1101/gad.14.6.655

10.1101/gad.918201

10.1101/gad.897901

10.1016/S0960-9822(98)70298-2

10.1016/S0092-8674(01)00361-0

10.1016/S0092-8674(00)00202-6

10.1093/emboj/17.5.1336

10.1016/S0092-8674(00)80528-0

10.1073/pnas.081076898

10.1128/MCB.21.11.3692-3703.2001

10.1083/jcb.200102093

10.1016/S1534-5807(01)00019-3

10.1126/science.278.5337.460

10.1073/pnas.231487598

Zachariae, 1999, Whose end is destruction: Cell division and the anaphase-promoting complex., Genes & Dev., 13, 2039, 10.1101/gad.13.16.2039

10.1126/science.282.5394.1721

10.1128/MCB.21.15.5190-5199.2001