2. The Main Idea
• The Cell Cycle is regulated by a
molecular control system
3. How often do cells
divide?
• Different types of cells divide at different times
– Skin cells divide frequently
– Liver cells divide infrequently
– Mature nerve and muscle cells do not divide at all
• These differences are the result of regulation
of these cells at the molecular level
4. What drives the
cell cycle?
• Very specific
chemical signals in
the cytoplasm
control the cell cycle
• This hypothesis was E.g. one cell in G1, while the
other was in mitosis
tested by fusing the
The G1 cell would immediately
nuclei of 2 cells
– Each cell was in a
different phase of the
cell cycle
enter mitosis
– Seems to support the idea
that chemicals in the
cytoplasm of the cell in
mitosis caused the G1 cell to
also go into mitosis
5.
6.
7. The Checkpoints
• The signals in
the cycle are
transmitted via
signal
transduction
pathways
9. The CELL CYCLE
CONTROL SYSTEM
• A set of
molecules that
operate in a cycle
to trigger and
coordinate the
events of the cell
cycle
10. The CELL CYCLE CONTROL
SYSTEM
• A good analogy is the timing device on a
washing machine
– Each step happens on it’s own
– Driven by an internal clock that tells it when to begin
each new step
– Regulated by both internal signals (tub is full of
water) and external signals (pushing the start
button)
11. CHECKPOINTS in the
Cell Cycle Control
System
• A critical control
point in the cell
cycle where the
cycle stops until
a go-ahead
signal is
received
12. The checkpoints
• The G1 checkpoint
seems to be an
especially important
one
– If the go-ahead signal is
received here, the cell
usually completes S, G2,
and M phase
– If not signal is received,
the cell goes into G0, a
non-dividing state
13. There are 3 major
checkpoints
• G1 checkpoint
• G2 checkpoint
• M checkpoint
15. The “chemicals” that
control the cell cycle
• 2 types of proteins:
– Cyclins
– Cyclin-dependent
kinases (Cdks)
• Remember a kinase is a
protein that
phosphorylates other
molecules
• These kinases are only
active when attached to
a cyclin protein
16. The “chemicals” that
control the cell cycle
• Cyclin levels rise a lot during interphase
• Cyclin levels fall quickly during mitosis
17. The “chemicals” that
control the cell cycle
• Peaks in the activity of cyclin correspond
to peaks in the activity of MPF
– M-phase promoting factor
– This protein bonds to cyclin & triggers the
passage of the cell from the G2 checkpoint
into mitosis
18. MPF
• Triggers other
protein kinases
• Stimulates the
breakdown of the
nuclear membrane
• Triggers the
breakdown of
cyclin
19. Examples of other
cell cycle regulators
1. A signal in the M phase checkpoint ensures
that all the chromosomes are properly
attached to the spindle fiber
1. Helps ensure that there are no missing or extra
chromosomes in the new cells
2. Another signal delays anaphase until all the
until all the spindles are attached to the
centrosomes
1. Once attached, another signal causes the
proteins holding the sister chromatids together to
break down
21. Cancer
• Cancer cells do not
respond normally to
the control
mechanisms
• These cells divide
excessively and
invade other tissues
22. Cancer
• Cells turn cancerous when a
single cell undergoes a
transformation (the process
that converts a normal cell to a
cancer cell)
• Normally, the immune system
finds and destroys transformed
Cancer cell
cells
(gray) being
• Cells that are not destroyed
may divide excessively and
attacked by
form a tumor - a mass of
immune system
abnormal cells
cells (green)
23. Cancer
• A tumor that stays at the original site
forms a lump called a benign tumor
• These usually do not cause problems
and can be removed surgically
Ready?…
26. Cancer
• Malignant tumors the cells become
invasive enough in
other tissues to
impair the functions
of organs
27. Cancer
• Cancerous cells also
become “loose” (lose
their attachment to
other cells) and are
carried into other
tissues in the blood
stream, where they start
new tumors
• This is called
metastasis
28. Cancer
• Cancer cells are
abnormal in that:
– Odd number of
chromosomes
– Disabled metabolism
– Nonfunctioning
metabolism
– Secrete signal molecules
that cause blood vessels
to grow toward a tumor
29. Treatments for Cancer
• High energy radiation
• Chemotherapy
– Drugs that interfere with the cell
cycle
• Taxol prevents cells from moving past
metaphase
• Many side effects due to the effect on
normal cells
• These treatments target cells
that are dividing rapidly
30. Causes of Cancer
• There are many
• All causes involve the alteration of
genes that help control the cell cycle