Essential Cell Biology 5th edition

642 CHAPTER 18 The Cell-Division Cycle
In this way, the cell dismantles itself quickly and cleanly, and its corpse is
rapidly taken up and digested by another cell.
Activation of the apoptotic program, like entry into a new stage of the cell
cycle, is usually triggered in an all-or-none fashion: once a cell reaches a
critical point along the path to destruction, it cannot turn back.
The Intrinsic Apoptotic Death Program Is Regulated by
the Bcl2 Family of Intracellular Proteins
All nucleated animal cells contain the seeds of their own destruction: in
these cells, inactive procaspases lie waiting for a signal to destroy the
cell. It is therefore not surprising that caspase activity is tightly regulated
to ensure that the death program is held in check until it is needed—
for example, to eliminate cells that are superfluous, mislocated, or badly
damaged.
The main proteins that regulate the activation of caspases are members
of the Bcl2 family of intracellular proteins. Some members of this protein
family promote caspase activation and cell death, whereas others
inhibit these processes. Two of the most important death-inducing family
members are proteins called Bax and Bak. These proteins—which are activated
in response to DNA damage or other insults—promote cell death
by inducing the release of the electron-transport protein cytochrome c
from mitochondria into the cytosol. Other members of the Bcl2 family
(including Bcl2 itself) inhibit apoptosis by preventing Bax and Bak from
releasing cytochrome c. The balance between the activities of pro-apoptotic
and anti-apoptotic members of the Bcl2 family largely determines
whether a cell lives or dies by apoptosis.
The cytochrome c molecules released from mitochondria activate initiator
procaspases—and induce cell death—by promoting the assembly of
a large, seven-armed, pinwheel-like protein complex called an apoptosome.
The apoptosome then recruits and activates a particular initiator
procaspase, which then triggers a caspase cascade that leads to apoptosis
(Figure 18−40).
Apoptotic Signals Can Also Come from Other Cells
Sometimes the signal to commit suicide is not generated internally, but
instead comes from a neighboring cell. Some of these extracellular signals
activate the cell death program by altering the activity of members
of the Bcl2 family of proteins. Others stimulate apoptosis more directly by
activating a set of cell-surface receptor proteins known as death receptors.
One particularly well-understood death receptor, called Fas, is present
on the surface of a variety of mammalian cell types. Fas is activated by
a membrane-bound protein, called Fas ligand, present on the surface of
specialized immune cells called killer lymphocytes. These killer cells help
regulate immune responses by inducing apoptosis in other immune cells
that are unwanted or are no longer needed—and activating Fas is one
way they do so. The binding of Fas ligand to its receptor triggers the
assembly of a death-inducing signaling complex, which includes specific
initiator procaspases that, when activated, launch a caspase cascade that
leads to cell death.
Animal Cells Require Extracellular Signals to Survive,
Grow, and Divide
In a multicellular organism, the fate of individual cells is controlled by
signals from other cells. Such communication ensures that a cell survives
only when it is needed and divides only when another cell is required,
either to allow tissue growth or to replace cell loss.