Molecular Biology of the Cell by Bruce Alberts, Alexander Johnson, Julian Lewis, David Morgan, Martin Raff, Keith Roberts, Peter Walter by by Bruce Alberts, Alexander Johnson, Julian Lewis, David Morg

CYTOKINESIS
1003
NUCLEAR
DIVISIONS
NUCLEAR
MIGRATION
TO CORTEX
CELL
BOUNDARIES
START TO
FORM
CELLULARIZATION
COMPLETED
(A)
fertilized egg
many nuclei in
a syncytium
cuticle
plasma
membrane
Figure 17–51 Mitosis without cytokinesis in the early Drosophila
embryo. (A) The first 13 nuclear divisions occur synchronously and without
cytoplasmic division to create a large syncytium. Most of the nuclei migrate
to the cortex, and the plasma membrane extends inward and pinches
off to surround each nucleus to form individual cells in a process called
cellularization. (B) Fluorescence micrograph of multiple mitotic spindles in
a Drosophila embryo before cellularization. The microtubules are stained
green and the centrosomes red. Note that all the nuclei go through the
cycle synchronously; here, they are all in metaphase, with the unlabeled
chromosomes seen as a dark band at the spindle equator. (B, courtesy of
Kristina Yu and William Sullivan.)
cell-cycle control system to a state of Cdk inactivity as the cell prepares to enter a
new cell cycle. In most cells, this state of Cdk inactivity generates a G 1 gap phase,
during which the cell grows and monitors its environment before committing to
a new cell cycle.
In early animal embryos, the inactivation of M-Cdk in late mitosis is due
almost entirely to the action of Cdc20–APC/C, discussed earlier. Recall, however,
that M-Cdk stimulates Cdc20–APC/C activity. Thus, the destruction of M-cyclin
in late mitosis soon leads to the inactivation of all APC/C activity in an embryonic
cell. This APC/C inactivation immediately after mitosis is especially useful
in rapid embryonic cell cycles, as it allows the cell to quickly begin accumulating
new M-cyclin for the next cycle (Figure 17–52A).
Rapid cyclin accumulation immediately after mitosis is not useful, however, for
cells in which a G 1 phase is needed to allow control of entry into the next cell cycle.
These cells employ several mechanisms to prevent Cdk MBoC6 reactivation m17.59/17.51 after mitosis.
One mechanism uses another APC/C-activating protein called Cdh1, mentioned
earlier as a close relative of Cdc20 (see Table 17–2). Although both Cdh1
and Cdc20 bind to and activate the APC/C, they differ in one important respect.
Whereas M-Cdk activates the Cdc20–APC/C complex, it inhibits the Cdh1–APC/C
complex by directly phosphorylating Cdh1. As a result of this relationship, Cdh1–
APC/C activity increases in late mitosis after the Cdc20–APC/C complex has initiated
the destruction of M-cyclin. M-cyclin destruction therefore continues after
mitosis: although Cdc20–APC/C activity has declined, Cdh1–APC/C activity is
high (Figure 17–52B).
A second mechanism that suppresses Cdk activity in G 1 depends on the
increased production of CKIs, the Cdk inhibitor proteins discussed earlier. Budding
yeast cells, in which this mechanism is best understood, contain a CKI protein
called Sic1, which binds to and inactivates M-Cdk in late mitosis and G 1 (see
Figure 17–52 The creation of a G 1 phase by stable Cdk inhibition after
mitosis. (A) In early embryonic cell cycles, Cdc20–APC/C activity rises at
the end of metaphase, triggering M-cyclin destruction. Because M-Cdk
activity stimulates Cdc20–APC/C activity, the loss of M-cyclin leads to APC/C
inactivation after mitosis, which allows M-cyclins to begin accumulating again.
(B) In cells that have a G 1 phase, the drop in M-Cdk activity in late mitosis
leads to the activation of Cdh1–APC/C (as well as to the accumulation of Cdk
inhibitor proteins; not shown). This ensures a continued suppression of Cdk
activity after mitosis, as required for a G 1 phase.
(B)
(A) embryonic cells with no G 1 phase
M-cyclin level
M
(B) cells with G 1 phase
M-cyclin level
10 µm
Cdc20–APC /C activity
S
Cdc20–APC /C activity
Cdh1–APC /C
activity keeps
M-cyclin level
low in G 1
M G 1