Cyclins are synthesized and degraded in a cyclic manner and with correlation to the cell cycle
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Transcript of Cyclins are synthesized and degraded in a cyclic manner and with correlation to the cell cycle
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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
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sea urchin! sea urchin!
Cyclins are indeed degraded
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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
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Overview of the frog life cycle
1 mmsperm tadpole feeds, grows and becomes an adult frog
OOCYTE GROWS WITHOUT DIVIDING(MONTHS) FERTILIZATION
FERTILIZED EGG DIVIDES WITHOUT GROWING(HOURS)
Xenopus laevis
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The maturation of frog eggs
Progesterone
8 months!
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Yoshio Masui, 1971The Maturation of Frog Eggs
Progesterone
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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
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MPF activity peaks right before mitosis and drops before mitosis is completed
Checking MPF activity from different cells and different stages
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Purification of MPFThe birth of cyclin dependent kinases
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MPF is a heterodimer of CDK and cyclin
Cyclin-CDK complexes control the cell cycle clock
MPF promotes entry to mitosis and then disappears
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Now performsa cell cycle function
CDKs form heterodimers with cyclins and become active kinases
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Yeasts have one CDK and several cyclinsHumans have 4 CDKs and 4 cyclins
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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
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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
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The Nobel Prize in Physiology or Medicine, 2001“For their discovery of key regulators of the cell cycle”
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CDKs are the major activators/inhibitors controlling the cell cycle
How are they regulated?
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Mechanisms of CDKs regulation
1. Abundance of cyclins
2. CDK phosphorylation
3. Binding to CKIs (inhibitory proteins)
CDK
Cyclin
active
p21+
inactiveCDK
Cyclinp21
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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
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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
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Ubiquitination
Proteasome
E1, E2, and E3 are all importantE3 ligase is the proteins that
conferss specificity to the target