Essential Cell Biology 5th edition

644 CHAPTER 18 The Cell-Division Cycle
Figure 18−41 Cell death can help adjust
the number of developing nerve cells to
the number of target cells they contact. If
more nerve cells are produced than can be
supported by the limited amount of survival
factor released by the target cells, some
cells will receive insufficient amounts of
survival factor to keep their suicide program
suppressed and will undergo apoptosis.
This strategy of overproduction followed
by culling can help ensure that all target
cells are contacted by nerve cells and that
the “extra” nerve cells are automatically
eliminated.
nerve
cell
body
nerve
cell
axon
nerve cells
target cells
CELL DEATH
HELPS MATCH
NUMBER OF
NERVE CELLS
TO NUMBER OF
TARGET CELLS
survival factor
released by target cells
apoptotic
nerve cells
nerve cells that receive enough survival factor live, while the others die
by apoptosis. In this way, the number of surviving nerve cells is automatically
adjusted to match the number of cells with which they connect
(Figure 18−41). A similar dependence on survival signals from neighboring
cells is thought to help control cell numbers in other tissues, both
during development and in adulthood.
ECB4 e18.41/18.41
Survival factors usually act through cell-surface receptors. Once activated,
the receptors turn on intracellular signaling pathways that keep
the apoptotic death program suppressed, usually by regulating members
of the Bcl2 family of proteins. Some survival factors, for example,
increase the production of Bcl2, a protein that suppresses apoptosis
(Figure 18−42).
CYTOSOL
NUCLEUS
survival factor
mRNA
activated
receptor
activated
transcription
regulator
Bcl2 gene
Bcl2 protein
APOPTOSIS BLOCKED
Figure 18−42 Survival factors often
suppress apoptosis by regulating Bcl2
family members. In this case, the survival
factor binds to cell-surface receptors that
activate an intracellular signaling pathway,
which in turn activates a transcription
regulator in the cytosol. This protein moves
ECB5 e18.42/18.42
to the nucleus, where it activates the gene
encoding Bcl2, a protein that inhibits
apoptosis (see also Figure 16–33).
Mitogens Stimulate Cell Division by Promoting Entry into
S Phase
Most mitogens are secreted signal proteins that bind to cell-surface
receptors. When activated by mitogen binding, these receptors initiate
various intracellular signaling pathways (discussed in Chapter 16) that
stimulate cell division. As we saw earlier, these signaling pathways act
mainly by releasing the molecular brakes that block the transition from
the G 1 phase of the cell cycle into S phase (see Figure 18−14).
Most mitogens have been identified and characterized by their effects
on cells in culture. One of the first mitogens identified in this way was
platelet-derived growth factor, or PDGF, the effects of which are typical
of many others discovered since. When blood clots form (in a wound,
for example), blood platelets incorporated in the clots are stimulated to
release PDGF. PDGF then binds to receptor tyrosine kinases (discussed in
Chapter 16) in surviving cells at the wound site, stimulating these cells to
proliferate and help heal the wound. In a similar way, if part of the liver is
lost through surgery or acute injury, a mitogen called hepatocyte growth
factor helps stimulate the surviving liver cells to proliferate.
Growth Factors Stimulate Cells to Grow
The growth of an organ—or an entire organism—depends as much on
cell growth as it does on cell division. If cells divided without growing,
they would get progressively smaller, and there would be no increase
in total cell mass. In single-celled organisms such as yeasts, both cell
growth and cell division require only nutrients. In animals, by contrast,
both cell growth and cell division depend on signals from other cells.
Cell growth, unlike cell division, does not depend on the cell-cycle control
system. Indeed, many animal cells, including nerve cells and most
muscle cells, do most of their growing after they have terminally differentiated
and permanently stopped dividing.