cyclins are synthesized and degraded in a cyclic manner and with correlation to the cell cycle...
Post on 19-Dec-2015
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Cyclins are synthesized and degraded in a cyclic manner and with correlation to the cell cycle
ProteinLevel
Time
cyclin A cyclin B
M M M
Something needs to go away in order for the cell cycle to proceed
Yeast genetics Needed for promoting cells through the cell cycle
CDK
Biochemistry in sea urchinAppear in correlation with the cell cycle
Cyclin
Time to bring them together
Overview of the frog life cycle
1 mm
spermtadpole feeds, grows
and becomes an adult frog
OOCYTE GROWS WITHOUT DIVIDING(MONTHS) FERTILIZATION
FERTILIZED EGG DIVIDES WITHOUT GROWING(HOURS)
Xenopus laevis
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
MPF activity peaks right before mitosis and drops before mitosis is completed
Checking MPF activity from different cells and different stages
MPF is a heterodimer of CDK and cyclin
Cyclin-CDK complexes control the cell cycle clock
MPF promotes entry to mitosis and then disappears
MPF is a heterodimer of CDK and cyclin active in the entry into mitosis
- 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
X
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”
Mechanisms of CDKs regulation
1. Abundance of cyclins
2. CDK phosphorylation
3. Binding to CKIs (inhibitory proteins)
CDK
Cyclin
active
p21+
inactiveCDK
Cyclinp21
ProteinLevel
Time
cyclin A cyclin B
M M M
Mechanisms of CDKs regulation
1. Abundance of cyclins- cyclins need to appear- cyclins need to disappear
A destruction box targets degradation of the cyclin
Destruction is achieved through ubiquitination
Mutations in the box = no degradation = cyclins always there = cell cycle cannot be completed