L312Spring 2007Lecture 20Drummond April 3

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L312/Spring 2007 Lecture 20 Drummond April 3
For today Begin Ch. 19 Mitosis and
cytokinesis Old exams/drawing exercises
available after class Last time Apoptosis
(Programmed Cell Death PCD) (an ordered,
irreversible cascade) virtually every major
structure is degraded within intact
PM caspase cascade is initiated (caspases X,
Y and Z) what are these? small protein
regulators (bax, bak) form membrane
channels, mediate cytochrome c release
from mitochondria (bax, bak are bcl-2
family members) bcl-2 inhibits apoptosis,
prolongs survival window Today distinguish
between mitogens, growth factors and survival
factors mitogens activate cyclins,
phosphorylate Rb (among others) growth
factors modulate protein degradation/synthesis
survival factors block apoptosis for
specific cells Mitosis (high school biology,
revisited) with emphasis on molecular
details special attention to roles and
structures of filaments DNA
compaction cellular structures
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Apoptosis revisited What happens to the
mitochondria during apoptosis? What are the roles
of the bcl-2 family of proteins?
Why have a cascade?
Why proenzymes (and not regulated by
phosphorylation?)
Why here first?
What does bcl-2 do?
What is the possible contribution of requiring an
aggregation of caspase?
Bcl-2
(inhibitor)
Another key System is always in place
mediators
bax
bak
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Classes of extracellular signals that control
growth and apoptosis

• Death factors
• Binds transmembrane receptor and induces
  apoptosis
• or necrosis (TNF, death ligands)
• Mitogens
• Stimulate cell division (interfere with cyclin
  control)
• 3. Growth factors
• Stimulate growth in cell mass
• (upregulate protein synthesis or prevent
  degradation)
• 4. Survival factors
• Suppress the initiation of apoptosis
• (might induce bcl-2, for example)

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How do mitogens promote cell proliferation?
Rb retinoblastoma gene/protein What might be a
mutation that causes cancer?
Remember generic switch story
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Growth factors stimulate growth but not
proliferation
How could a cell be stimulated to
continue growing but not divide?
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Growth factors regulate protein and cell
component synthesis and degradation
Cell growth as a steady-state phenomenon
(What else?)
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What happens when you inhibit a block inhibition
of growth?
Myostatin normally blocks cellular growth
(NOT proliferation)
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Review of the stages of mitosis
Cyclin/cdk, feedback loop
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A few details for each phase
Pay close attention to each of the structures
Track DNA/ centrosomes
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How are these structures distinct from interphase
structures?
Track nuclear envelope/lamina
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Why must the nuclear envelope break down?
Ask how are these changes effected?
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Key to metaphase alignment of kinetochores
track DNA and microtubules role of dynamic
instability here?
Whats the difference between an astral and
kinetochore microtubule? What is the role of each
structure, and how do they differ from interphase
structures?
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Key events during anaphase
Why do chromosomes move? (what happens to the
microtubules). Why do spindle poles move? How
could this be? Why did the chromosomes separate
here? Is it by force?
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Why does the nuclear envelope re-form so
soon? What else is happening here?
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How are organelles excluded from the
nucleus? What happens to the microtubules?
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Chromatin condenses during interphase
Why are DNA strands held together after
synthesis? (2 key reasons) what is the
contribution of the histone code here?
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The centrosome duplicates and migrates entering
mitosis
How are these microtubules Different from
interphase MTs?
The nuclear hug
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Two new classes of microtubules form from highly
dynamic structures
Dynamic instability Why?
What are MAPs and what happens to them in mitosis?
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Nuclear envelope breaks down at the onset of
prometaphase (allows 1-50 microtubules to find
chromatids at specific sites)
Third class of microtubules kinetochore
microtubules What is the importance of the highly
dynamic microtubule structure in forming
attachments?
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Microtubules are stabilized by attachment to the
centromere
What is the centromere?
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Chromosomes near metaphase note relative sizes
DNA blue Kinetochores red Microtubules green
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Chromosomes separate at anaphase
Specific proteases degrade cohesins APC (anaphase
promoting complex) is cell cycle (cyclin)
regulated and promotes progression--how?
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The role of APC in cohesin degradation (one of
many roles)