cyclins are synthesized and degraded in a cyclic manner and with correlation to the cell cycle
DESCRIPTION
Protein Level. cyclin A. cyclin B. Time. M. M. M. Cyclins are synthesized and degraded in a cyclic manner and with correlation to the cell cycle. Something needs to go away in order for the cell cycle to proceed. Cyclins are indeed degraded. sea urchin!. sea urchin!. CDK. - PowerPoint PPT PresentationTRANSCRIPT
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
sea urchin! sea urchin!
Cyclins are indeed degraded
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 mmsperm tadpole feeds, grows and becomes an adult frog
OOCYTE GROWS WITHOUT DIVIDING(MONTHS) FERTILIZATION
FERTILIZED EGG DIVIDES WITHOUT GROWING(HOURS)
Xenopus laevis
The maturation of frog eggs
Progesterone
8 months!
Yoshio Masui, 1971The Maturation of Frog Eggs
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
MPF activity peaks right before mitosis and drops before mitosis is completed
Checking MPF activity from different cells and different stages
Purification of MPFThe birth of cyclin dependent kinases
MPF is a heterodimer of CDK and cyclin
Cyclin-CDK complexes control the cell cycle clock
MPF promotes entry to mitosis and then disappears
Now performsa cell cycle function
CDKs form heterodimers with cyclins and become active kinases
Yeasts have one CDK and several cyclinsHumans have 4 CDKs and 4 cyclins
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”
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)
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
Ubiquitination
Proteasome
E1, E2, and E3 are all importantE3 ligase is the proteins that
conferss specificity to the target