Transcript Cell Cycle II

Cyclins are synthesized and degraded in a cyclic
manner and with correlation to the cell cycle
Protein
Level
cyclin A
cyclin B
Time
M
M
M
Something needs to go away in order for the
cell cycle to proceed
Cyclins are indeed degraded
sea urchin!
sea urchin!
CDK
Yeast genetics
Needed for promoting cells through the cell cycle
Cyclin
Biochemistry in sea urchin
Appear in correlation with the cell cycle
Time to bring them together
Overview of the frog life cycle
Xenopus laevis
OOCYTE GROWS WITHOUT DIVIDING
(MONTHS)
FERTILIZATION
FERTILIZED EGG DIVIDES WITHOUT GROWING
(HOURS)
1 mm
sperm
tadpole feeds, grows
and becomes an adult frog
The maturation of frog eggs
Progesterone
8 months!
The Maturation of Frog Eggs
Yoshio Masui, 1971
Progesterone
MPF = Maturation Promoting Factor
Injections of M-phase mitotic cells from different
organisms also promoted Xenopus oocyte
maturation, showing that MPF is a general factor in
promoting mitosis
Checking MPF activity from different cells and
different stages
MPF activity peaks
right before
mitosis and drops
before mitosis is
completed
Purification of MPF
The birth of cyclin dependent kinases
MPF is a heterodimer of CDK and cyclin
MPF promotes entry to
mitosis and then disappears
Cyclin-CDK complexes
control the cell cycle clock
CDKs form heterodimers with cyclins and
become active kinases
Now performs
a cell cycle function
Yeasts have one CDK and several cyclins
Humans have 4 CDKs and 4 cyclins
MPF is a heterodimer of CDK and cyclin active
in the entry into mitosis
X
- Cyclin-Cdk complexes function in different phases
- G1/S-Cdk complexes commit the cell to a new cell cycle
- S-Cdk complexes promote S phase
- M-Cdk complexes allow entry into mitosis
- M-Cdk complexes are removed before anaphase
Example: cycB-Cdk1 appears in mitosis,
phosphorylates lamin and leads to nuclear envelope
breakdown during early mitosis
cycB-Cdk1 will be degraded during mitosis to allow
formation of a new nuclear envelop breakdown
during telophase
The Nobel Prize in Physiology or Medicine, 2001
“For their discovery of key regulators of the cell cycle”
CDKs are the major activators/inhibitors
controlling the cell cycle
How are they regulated?
Mechanisms of CDKs regulation
1. Abundance of cyclins
2. CDK phosphorylation
3. Binding to CKIs (inhibitory proteins)
active
inactive
CDK
CDK
Cyclin
+
p21
Cyclin
p21
Mechanisms of CDKs regulation
1. Abundance of cyclins
- cyclins need to appear
- cyclins need to disappear
Protein
Level
cyclin A
cyclin B
Time
M
M
M
A destruction box targets degradation
of the cyclin
Mutations in the box = no degradation = cyclins
always there = cell cycle cannot be completed
Destruction is achieved through
ubiquitination
Ubiquitination
E1, E2, and E3 are all important
E3 ligase is the proteins that
conferss specificity to the
target
Proteasome