| | |  | | | | Record from Web of Science® | | | | | | |
| Calcineurin is required to release Xenopus egg extracts from meiotic M phase |
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| Author(s): Mochida S (Mochida, Satoru), Hunt T (Hunt, Tim) |
| Source: NATURE Volume: 449 Issue: 7160 Pages: 336-+ Published: SEP 20 2007 |
| Times Cited: 25 References: 32 |
| Abstract: Fertilization induces a transient increase in cytoplasmic Ca2+ concentration in animal eggs that releases them from cell cycle arrest in the second meiotic metaphase(1). In frog eggs, Ca2+ activates Ca2+/calmodulin-activated kinase, which inactivates cytostatic factor(2-5), allowing the anaphase-promoting factor to turn on and ubiquitinate cyclins and securin, which returns the cell cycle to interphase(6). Here we show that the calcium-activated protein phosphatase calcineurin(7) is also important in this process. Calcineurin is transiently activated after adding Ca2+ to egg extracts, and inhibitors of calcineurin such as cyclosporin A (ref. 8) delay the destruction of cyclins, the global dephosphorylation of M-phase-specific phosphoproteins and the re-formation of a fully functional nuclear envelope. We found that a second wave of phosphatase activity directed at mitotic phosphoproteins appears after the spike of calcineurin activity. This activity disappeared the next time the extract entered M phase and reappeared at the end of mitosis. We surmise that inhibition of this second phosphatase activity is important in allowing cells to enter mitosis, and, conversely, that its activation is required for a timely return to interphase. Calcineurin is required to break the deep cell cycle arrest imposed by the Mos-MAP (mitogen-activated protein) kinase pathway(4,5,9), and we show that Fizzy/Cdc20, a key regulator of the anaphase-promoting factor(6), is an excellent substrate for this phosphatase. |
| Document Type: Article |
| Language: English |
| Reprint Address: Hunt, T (reprint author), Imperial Canc Res Fund, Clare Hall Labs, London Res Ctr, Canc Res UK, S Mimms EN6 3LD, Herts England |
Addresses:
1. Imperial Canc Res Fund, Clare Hall Labs, London Res Ctr, Canc Res UK, S Mimms EN6 3LD, Herts England |
| Publisher: NATURE PUBLISHING GROUP, MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND |
| Subject Category: Multidisciplinary Sciences |
| IDS Number: 211XP |
| ISSN: 0028-0836 |
| DOI: 10.1038/nature06121 |
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