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29 CELL CYCLE AND GROWTH REGULATION (Full Edition)
20 Exit from mitosis is controlled by the location of Cdc14
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During interphase the phosphatase Cdc14 is held in the nucleolus.
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When a spindle pole body migrates into the bud of S. cerevisiae, it carries the protein Tem1.
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Tem1 is a monomeric G protein that is activated by the local concentration of the exchange factor Lte1 in the bud.
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Activation of Tem1 triggers release of Cdc14.
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The action of Cdc14 triggers exit from mitosis.
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Figure 29.37
Cdc14 dephosphorylates both Cdh1 and Sic1. The first
action leads to activation of the APC that degrades mitotic cyclins.
The second action enables Sic1 to reversibly inactivate mitotic cyclins.
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The key event in leaving mitosis is the activation of the phosphatase
Cdc14 (908). Figure 29.37
shows that during interphase, Cdc14 is sequestered in the nucleolus
(because it binds to a nucleolar protein variously called
RENT/Cfi1/Net1) (1202; 1203). When it is localized in
the nucleolus, it cannot find any of its substrates, and therefore is
inactive. When it is released from the nucleolus, it acts on (at least)
two substrates. Dephosphorylation of Cdh1 is necessary to activate the
APCCdh1 complex. And dephosphorylation of Sic1 enables it to
inactivate mitotic cyclins. This is another example of belts and braces
in cell cycle control, where parallel pathways lead to the same outcome.
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What triggers the release of Cdc14 from
the nucleolus? The pathway for leaving mitosis has many genes, and
genetic relationships suggest that two key components are the
GTP-binding protein Tem1 and the exchange factor Lte1. Like other
monomeric G proteins, Tem1 is active when bound to GTP, and inactive
when bound to GDP. The exchange factor activates it by causing bound
GDP to be replaced with GTP (see G proteins). The ability of
Lte1 to activate Tem1 is controlled in an interesting way by the
locations of the two components in the yeast cell.
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Figure 29.38
Exit from mitosis is triggered when the Tem1 that is
localized on a spindle poly body migrates into the bud where Lte1 is
localized.
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Recall that S. cerevisiae has an asymmetrical
division in which the daughter cell forms as a bud of the mother cell (see Figure 29.10).
Lte1 protein is present throughout the cell cycle, and when the bud
forms at the beginning of S phase, the Lte1 is localized in it. By
contrast, Tem1 is synthesized only at late S phase. At mitosis, the
Tem1 is localized with one of the spindle pole bodies (the structures
identifying the ends of the spindle where microtubules are nucleated). Figure 29.38
shows that this is the spindle pole body that migrates into the bud!
When Tem1 arrives in the concentration of Lte1 in the bud, it is
activated (1204). This triggers the release of Cdc14
from the nucleolus, which in turn triggers exit from mitosis.
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Last Revised on 10-18-2000
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908 Shirayama, M. et al.
(1999).
APCCDC20 promotes exit from mitosis by destroying the anaphase inhibitor Pds1 and cyclin Clb5.
Nature 402, 203-207.
PubMed Journal
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1202 Shou, W., Seol, J. H., Shevchenko, A.,
Baskerville, C., Moazed, D., Chen, Z. W., Jang, J., Shevchenko, A.,
Charbonneau, H., and Deshaies, R. J. (1999). Exit from mitosis is
triggered by Tem1-dependent release of the protein phosphatase Cdc14
from nucleolar RENT complex. Cell 97, 233-244. PubMed Journal
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1203 Straight, A. F., Shou, W., Dowd, G. J., Turck, C. W., Deshaies, R. J., Johnson, A. D., and Moazed, D.
(1999).
Net1, a Sir2-associated nucleolar protein required for rDNA silencing and nucleolar integrity.
Cell 97, 245-256.
PubMed Journal
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1204 Bardin, A. J., Visintin, R., and Amon, A.
(2000).
A mechanism for coupling exit from mitosis to partitioning of the nucleus.
Cell 102, 21-31.
PubMed Journal
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©Jones and Bartlett Publishers (2007)
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