Essential Cell Biology 5th edition

The Cell-Cycle Control System
617
S cyclin
M cyclin
Figure 18−8 Distinct Cdks associate with
different cyclins to trigger the different
events of the cell cycle. For simplicity,
only two types of cyclin–Cdk complexes are
shown: one that triggers S phase and one
that triggers M phase.
S
G 1
S cyclin M cyclin
G 2
M
G 1
active S-Cdk
active M-Cdk
are shown in Figure 18−8. Another group of cyclins, called G 1 cyclins,
act earlier in G 1 and bind to other Cdk proteins to form G 1 -Cdks, which
help drive the cell through G 1 toward S phase. We see later that the formation
of these G 1 -Cdks in animal cells usually depends on extracellular
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signal molecules that stimulate cells to divide. The names of the main
cyclins and their Cdks are listed in Table 18−2.
Each of these cyclin–Cdk complexes phosphorylates a different set of target
proteins in the cell. G 1 /S-Cdks, for example, phosphorylate regulatory
proteins that activate transcription of genes required for DNA replication.
By activating different sets of target proteins, each type of complex triggers
a different transition step in the cell cycle.
Cyclin Concentrations Are Regulated by Transcription
and by Proteolysis
As discussed in Chapter 7, the concentration of a given protein in the cell
is determined by the rate at which the protein is synthesized and the rate
at which it is degraded. Over the course of the cell cycle, the concentration
of each type of cyclin rises gradually and then falls abruptly (see
Figure 18−8). The gradual increase in cyclin concentration stems from
continued transcription of cyclin genes and synthesis of cyclin proteins,
whereas the rapid fall in cyclin concentration is precipitated by a fullscale
targeted destruction of the protein.
The abrupt degradation of M and S cyclins partway through M phase
depends on a large enzyme called—for reasons that will become clear
later—the anaphase-promoting complex or cyclosome (APC/C). This
complex tags these cyclins with a chain of ubiquitin. As discussed in
Chapter 7, proteins marked in this way are directed to proteasomes where
they are rapidly degraded (see Figure 7−43). The ubiquitylation and degradation
of the cyclin returns its Cdk to an inactive state (Figure 18−9).
TABLE 18−2 THE MAJOR CYCLINS AND CDKS OF VERTEBRATES
Cyclin–Cdk Complex Cyclin Cdk Partner
G 1 -Cdk cyclin D* Cdk4, Cdk6
G 1 /S-Cdk cyclin E Cdk2
S-Cdk cyclin A Cdk2
M-Cdk cyclin B Cdk1
*There are three forms of cyclin D in mammals (cyclins D1, D2, and D3).