Cycle Cell II Regulation
Ch. 12 pp. 238-243
Growth for the sake
of growth is the
ideology of the cancer
cell.
Edward Abbey
I. The cell cycle clock (or engine)
A series of activation and deactivation reactions of
proteins (cyclins and cyclin-dependent kinases) that
pace the cell cycle.
Timing of phosphorylations, dephosphorylations, protein
synthesis and degradation is critically important.
Checkpoints are three periods when intercellular
signals determine whether to stop, or let the clock
run.
Three checkpoints and their assessments
Or = M checkpoint
Or = Start
p53
Three checkpoints:
Time
G1
Late in G1
Function
Alternative
Determine if DNA
Enter G0 state
synthesis should begin
G2 G2-M border Determine if Mitosis
DNA
should begin
Stop for
repair
M
Mid Mitosis
Determine if Mitosis Stop for
csome
Know this table
should be completed attachment
Experimental analysis of cell cycle regulation
1. Experiments showing that
_________________________________________.
Fig. 12.13 shows an experiment in which one cell in M
and one cell in G1 were fused. The M cell cytoplasm
caused premature condensation of chromosomes in the
earlier G1 stage nucleus
What does this indicate about the Start checkpoint?
The real data show this:
Results of cell
fusion shown in
previous slide in
which G1
nucleus
chromosomes
are prematurely
condensed and
appear long and
thin upon
exposure to
M phase cell
cytoplasm
Would the
prematurely
condensed
chromosomes
be one
chromatid or
two?
Are there other interpretations of the experiment?
Another example is from
somatic cell nuclear
transplantation
(Fig. 20.18).
Here the egg cell
cytoplasm tells the
transplanted nucleus
what to do (in this case
undergo embryonic
division and
differentiation again).
2. Except for the cyclins regulatory proteins in the
cytoplasm are already present and need only to have
cycles of activation and deactivation.
Cyclins were discovered as proteins whose __________
_____________________________________
Picture 3
They were first
discovered in
embryonic
cell division.
You do not have to know the details
in the figure.
Furthermore cyclin abundance correlated
with a particular kinase activity (Mitosispromotion factor or MPF) because it was
part of the MPF molecule
What label
and what
molecule
would be
used to
measure
kinase
activity?
MPF is made of a Cdk
(cyclin-dependent
kinase) and cyclin. The
Cdk alone is not an
active kinase.
Main point for cell
cycle regulation:
_________________
_________________ to
move the cell through
the cycle.
MPFs functions to
phosphorylate proteins of mitosis including those for:
-_______ _________ thus causing nuclear
envelope breakdown
-Chromosome condensation
-Spindle formation
Synonyms for MPF: Same protein, and function but
different names.
Mitosis-Promotion Factor
M-phase-promoting Factor
Maturation-Promotion Factor
MPFs functions to
phosphorylate proteins of mitosis including those for:
- nuclear laminins thus causing nuclear
envelope breakdown
-Chromosome condensation
-Spindle formation
Synonyms for MPF: Same protein, and function but
different names.
Mitosis-Promotion Factor
M-phase-promoting Factor
Maturation-Promotion Factor
Multiple cyclins and
cdks are used in
somatic cells. Which
cyclin and cdk
is which MPF?
You do not have to
know these extra
Cyclin/cdks.
Sometimes the kinase is named cdc (for cell division
cycle) protein.
Here the
cdc is the
same but
the cyclins
differ.
3. Proteins that inhibit MPF were
discovered.
Picture 3
P27 inhibits the cell cycle by
________________________________
Mice without the p27 protein (brown) are larger
than littermates with the p27 protein (white)
This result fits with the hypothesis that p27 loss would
increase the number of cell cycles (i.e. more cells form).
The thymus (an immune system gland ) of the p27 knockout mice is much larger.
II. Loss of control in cancer cells
A. Three major phenotypic changes in cancer cells.
Progressively about 5 genes are mutated resulting in
transformation (=conversion of normal to cancer
cell):
1. Loss of checkpoint controls (e.g. p27 loss, the ras Gprotein continually activated, continued M when DNA is
still damaged, and many more).
2. __________: Unlike normal cells that can only divide
a set number of times, cancer cells can continually
divide.
3. Loss of adhesion dependence and gain of
Normally in culture cell
motility.
growth slows as a result
of cell-cell contact (not
as a result of running
out of nutrients).
Describe these cancer
cells phenotype?
Progression of a breast cancer to the metastatic
stage (Fig. 12.20)
Benign tumor
Malignant tumor
Checkpoint loss Adhesion loss
and immortality
gain
Motility gain
What is a prediction from the hypothesis that about 5
genes must be mutated for a cancer to develop?
A. Dividing cells in the body are less likely to form
cancers.
B. The incidence of cancer should increase with age.
C. Cancers form more often than if only one gene
mutation were necessary to form them.
D. A and B above are correct.
An application of basic biochemical
pathway information in cancer detection:
Tumors are hard to detect especially when they are
small.
Most cancer cells, however, use glycolysis much more
than do normal cells (this is called the Warburg
effect).
1.Which molecule (s) would accumulate in cancer cells
more than in normal cells and could be used for
detection?
2. What would be the ideal characteristic of this
molecule?
3.How can that molecule be visualized in the body?
Principle
behind
PET(positron
imaging
technology)
imaging is that
a labeled
glucose
becomes
phosphorylated
and trapped
within the cell
where it
accumulates.
Not on exam III
Normal PET scans showing high activity
in brain, heart and bladder. (Note that brain is a
very heavy user of glucose, almost exclusively).
Bladder accumulates
labeled glucose
because it is being
excreted by kidneys.
Picture 3
Hodgkins lymphoma
PET image showing
dark masses in chest
where metastatic
cancer cells are and
can then be targeted
for radiation
treatment.
Stem cells
These are rare, renewable (capable of division in the
adult), and immortal cells which give rise to
differentiated cells.
Blood stem cells
You do not have to know the cell types
shown here.
Study guide terms to know:
Cell cycle clock
G1checkpoint
G2 checkpoint
M checkpoint
Cyclin
Cyclin-dependent kinase (cdk)
MPF (Mitosis-promotion-factor)
P27
Benign tumor
Malignant tumor
Density-dependent inhibition
Anchorage independence
Metastasis
Stem cell