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

1018 Chapter 17: The Cell Cycle
EXTRACELLULAR FACTOR
GROWTH FACTOR
MITOGEN
EXTRACELLULAR FACTOR
CELL GROWTH
CELL DIVISION
CELL GROWTH
CELL DIVISION
CELL GROWTH
CELL DIVISION
(A) (B) (C)
Figure 17–65 Potential mechanisms for coordinating cell growth and division. In proliferating cells, cell size is maintained
by mechanisms that coordinate rates of cell division and cell growth. Numerous alternative coupling mechanisms are thought to
exist, and different cell types appear to employ different combinations of these mechanisms. (A) In many cell types—particularly
yeast—the rate of cell division is governed by the rate of cell growth, so that division occurs only when growth rate achieves
some minimal threshold; in yeasts, it is mainly the levels of extracellular nutrients that regulate the rate of cell growth and thereby
the rate of cell division. (B) In some animal cell types, growth and division can each be controlled by separate extracellular
factors (growth factors and mitogens, respectively), and cell size depends on the relative levels of the two types of factors.
(C) Some extracellular factors can stimulate both cell growth and cell division by simultaneously activating signaling pathways
that promote growth and other pathways that promote cell-cycle progression.
MBoC6 m17.66/17.65
Proliferating Cells Usually Coordinate Their Growth and Division
For proliferating cells to maintain a constant size, they must coordinate their
growth with cell division to ensure that cell size doubles with each division: if cells
grow too slowly, they will get smaller with each division, and if they grow too fast,
they will get larger with each division. It is not clear how cells achieve this coordination,
but it is likely to involve multiple mechanisms that vary in different organisms
and even in different cell types of the same organism (Figure 17–65).
Animal cell growth and division are not always coordinated, however. In many
cases, they are completely uncoupled to allow growth without division or division
without growth. Muscle cells and nerve cells, for example, can grow dramatically
after they have permanently withdrawn from the cell cycle. Similarly, the eggs of
many animals grow to an extremely large size without dividing; after fertilization,
however, this relationship is reversed, and many rounds of division occur without
growth.
Compared to cell division, there has been surprisingly little study of how cell
size is controlled in animals. As a result, it remains a mystery how cell size is determined
and why different cell types in the same animal grow to be so different in
size. One of the best-understood cases in mammals is the adult sympathetic neuron,
which has permanently withdrawn from the cell cycle. Its size depends on the
amount of nerve growth factor (NGF) secreted by the target cells it innervates; the
greater the amount of NGF the neuron has access to, the larger it becomes. It seems
likely that the genes a cell expresses set limits on the size it can be, while extracellular
signal molecules and nutrients regulate the size within these limits. The challenge
is to identify the relevant genes and signal molecules for each cell type.
Summary
In multicellular animals, cell size, cell division, and cell survival are carefully controlled
to ensure that the organism and its organs achieve and maintain an appropriate
size. Mitogens stimulate the rate of cell division by removing intracellular
molecular brakes that restrain cell-cycle progression in G 1 . Growth factors promote
cell growth (an increase in cell mass) by stimulating the synthesis and inhibiting
the degradation of macromolecules. To maintain a constant cell size, proliferating
cells employ multiple mechanisms to ensure that cell growth is coordinated with
cell division.
What we don’t know
• Progression through the cell cycle
depends on the phosphorylation
of hundreds of different proteins by
cyclin–Cdk complexes. What are the
molecular mechanisms ensuring that
these proteins are phosphorylated at
precisely the right time and place?
• During S phase, how are histones
and their modifying enzymes
controlled to replicate chromatin
structure on the duplicated DNA?
• What is the structural basis of
chromosome condensation, and
how is the process stimulated during
mitosis?
• What are the mechanisms by which
microtubule attachment and tension
are sensed at the kinetochore by the
components of the spindle assembly
checkpoint?
• How is cell growth coordinated with
cell division to ensure that cell size
remains constant?