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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

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972 Chapter 17: The Cell Cycle

The Cell-Cycle Control System Functions as a Network of

Biochemical Switches

Table 17–2 summarizes some of the major components of the cell-cycle control

system. These proteins are functionally linked to form a robust network, which

operates essentially autonomously to activate a series of biochemical switches,

each of which triggers a specific cell-cycle event.

When conditions for cell proliferation are right, various external and internal

signals stimulate the activation of G 1 -Cdk, which in turn stimulates the expression

of genes encoding G 1 /S- and S-cyclins (Figure 17–16). The resulting activation of

G 1 /S-Cdk then drives progression through the Start transition. By mechanisms

we discuss later, G 1 /S-Cdks unleash a wave of S-Cdk activity, which initiates

(A) control of proteolysis by APC /C

activating

subunit (Cdc20)

inactive APC /C

M-cyclin

polyubiquitin

chain

Cdk

active APC /C

ubiquitin ( )

+

E1

E2

ubiquitylation

enzymes

DEGRADATION

OF M-CYCLIN IN

PROTEASOME

(B) control of proteolysis by SCF

active

SCF

complex

F-box

protein

polyubiquitin

chain

kinase

P

P

DEGRADATION

OF CKI IN

PROTEASOME

Cdk inhibitor protein

(CKI)

ubiquitin ( )

+

E1

E2

ubiquitylation

enzymes

Figure 17–15 The control of proteolysis by APC/C and SCF during the cell cycle. (A) The

APC/C is activated in mitosis by association with Cdc20, which recognizes specific amino acid

sequences on M-cyclin and other target proteins. With the help of two additional proteins called

E1 and E2, the APC/C assembles polyubiquitin chains on the target protein. The polyubiquitylated

target is then recognized and degraded in a proteasome. (B) The activity of the ubiquitin ligase SCF

depends on substrate-binding subunits called F-box proteins, of which there are many different

types. The phosphorylation of a target protein, such as the CKI shown, allows the target to be

recognized by a specific F-box subunit.

MBoC6 m17.20/17.15

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