Essential Cell Biology 5th edition

Control of Cell Numbers and Cell Size
643
adaptor
protein
procaspase-9
RELEASE OF
CYTOCHROME C
ACTIVATION OF
ADAPTOR PROTEIN BY
CYTOCHROME C
ASSEMBLY
RECRUITMENT OF
PROCASPASE-9
MOLECULES
activated
Bax or Bak
molecules
cytochrome c
in intermembrane
space
apoptosome
ACTIVATION OF
PROCASPASE-9 WITHIN
APOPTOSOME
CASPASE CASCADE
LEADING TO APOPTOSIS
mitochondrion
APOPTOTIC
STIMULUS
Most of the extracellular signal molecules that influence cell survival, cell
growth, and cell division are either soluble proteins secreted by other
cells or proteins that are bound to the surface of other cells or to the
extracellular matrix. Although most act positively to stimulate one or
more of these cell processes, some act negatively to inhibit a particular
process. The positively acting signal proteins can be classified, on the
ECB5 e18.39/18.39
basis of their function, into three major categories:
1. Survival factors promote cell survival, largely by suppressing
apoptosis.
2. Mitogens stimulate cell division, primarily by overcoming the
intracellular braking mechanisms that block entry into the cell cycle
in late G 1 .
3. Growth factors stimulate cell growth (an increase in cell size
and mass) by promoting the synthesis and inhibiting the degradation
of proteins and other macromolecules.
These categories are not mutually exclusive, as many signal molecules
have more than one of these functions. Unfortunately, the term “growth
factor” is often used as a catch-all phrase to describe a protein with any
of these functions. Indeed, the phrase “cell growth” is frequently used
inappropriately to mean an increase in cell number, which is more correctly
termed “cell proliferation.”
In the following three sections, we examine each of these types of signal
molecules in turn.
Figure 18−40 Bax and Bak can trigger
apoptosis by releasing cytochrome c
from mitochondria. When Bak or Bax
proteins are activated by an apoptotic
stimulus, they aggregate in the outer
mitochondrial membrane, leading to
the release of cytochrome c into the
cytosol by an unknown mechanism.
Additional proteins in the mitochondrial
intermembrane space are released at the
same time—not shown. Cytochrome c then
binds to an adaptor protein, causing it to
assemble into a seven-armed complex
called the apoptosome. This complex
then recruits seven molecules of a specific
initiator procaspase (procaspase-9). The
procaspase-9 proteins become activated
within the apoptosome and then go on to
activate executioner procaspases in the
cytosol (as shown in Figure 18−39), leading
to a caspase cascade and apoptosis.
Survival Factors Suppress Apoptosis
Animal cells need signals from other cells just to survive. If deprived of
such survival factors, cells activate a caspase-dependent intracellular
suicide program and die by apoptosis. This requirement for signals from
other cells helps ensure that cells survive only when and where they are
needed. Many types of nerve cells, for example, are produced in excess
in the developing nervous system and then compete for limited amounts
of survival factors that are secreted by the target cells they contact. Those