Cell cycle regulation
Stages of asexual cell cycle
• 4 stages – G1, S, G2, M
Cell cycle is highly regulated, key checkpoints at
• G1 → S
• G2 → M
• Metaphase → Anaphase
Uncontrollable cell growth – lead to development of cancer
Cyclin variation is crucial for cell cycle progression
4 different types of cyclins
Cyclin B – levels increase during S phase, decreases
gradually through mitosis
Nuclear membrane starting to break down, shows
must be something in M phase cell, propelled into
mitosis even if it isn’t ready (spindle fibres forming,
chromosomes have to replicate before spindles are
formed)
If fuse cell like G1 with cell in later stage – will jump into the later stage whether that be M
or S
If use cytoplasm injection experiments, from later stage injected into earlier
cell, mitosis is triggered, has to be a positive signal to trigger it into mitosis –
aka a cyclin protein
3 types of proteins:
1. Cyclins
• Vary in level throughout cell cycle
• Bind & activate cdks
• Necessary but not always sufficient to activate the cdks
2. Cyclin dependent kinases (Cdks)
• Activation depends on cyclin binding + further phosphorylation
3. CAKs – Cdk activating kinases
• Need to be phosphorylated at thr of active site
Variation in cyclin B concentration
Cyclin itself can’t be responsible for entering into mitosis –
not a gradual entry
Cyclin has to reach threshold level before entering into
mitosis, will bind to cdk before MPF becomes active
, MPF
• MPF = mitosis/maturation promoting factor
• MPF is a kinase made up of a complex of cyclin & cdk
• Full activity of MPF is essential for entry into mitosis
• MPF also activates a pathway leading to its own degradation, so it disappears when
its job is done
Cyclin B is not sufficient to send cell into mitosis by itself, will
bind to cdk protein, complex = MPF, once binding = active
MPF, will send cell into mitosis
Active MPF= initiates sequence of events happens in
particular order
1. Nuclear envelope breaks down – enables regulatory
factors to move into nucleus, allows Spindle fibres growing
from poles to enter cells to make contact with kinetochores
2. Chromosomes shorten & thicken
3. Mitosis occurs
How MPF works (acts as a kinase to phosphorylate)
• MPF is a Cdk1 (Cdc2)-cyclin b complex
• It activates numerous proteins by phosphorylation
1. Lamins – causing the nuclear membrane to disperse, layer of proteins that form
undeath nuclear membrane when MPF phosphorylates lamins, structure of mesh
breaks down as does nuclear envelope
2. Condensins – promoting chromosome condensation (also cohesisns)
3. Histone H1 – Promoting chromatin condensation, 4 histones makes up protein
optima, linker histone, brings beads on string to a closer formation, so MPF trigger
this causes coiling & bringing together
4. Cdc 25 – a phosphatase that removes P from cdk1-cyclin B complex to fully activate
it
5. APC (anaphase promoting complex) – key role in metaphase → anaphase
checkpoint
Summary
Four main stages of the cell cycle (G1, S, G2, M).
• Three key checkpoints of the cell cycle (G1>S, G2>M, metaphase > anaphase).
• Cyclins and cdks form a complex called the Mitosis Promoting Factor (MPF).
• MPF acts by phosphorylating a number of proteins to allow entry into mitosis (or
meiosis!): lamins, condensins, histone H1, cdc25, APC
Lecture 2
NOTE: PRINT SLIDES 21-30
Notes for slides printed
On right has some activity but low on left highly active sends cell into mitosis
Orange = cyclin B, Blue = Cdk
3 phosphate groups on MPF – how cdc 25 & MPF work
One of phosphate groups activate MPF – one added b the CAK (Cdk activating kinases)
Stages of asexual cell cycle
• 4 stages – G1, S, G2, M
Cell cycle is highly regulated, key checkpoints at
• G1 → S
• G2 → M
• Metaphase → Anaphase
Uncontrollable cell growth – lead to development of cancer
Cyclin variation is crucial for cell cycle progression
4 different types of cyclins
Cyclin B – levels increase during S phase, decreases
gradually through mitosis
Nuclear membrane starting to break down, shows
must be something in M phase cell, propelled into
mitosis even if it isn’t ready (spindle fibres forming,
chromosomes have to replicate before spindles are
formed)
If fuse cell like G1 with cell in later stage – will jump into the later stage whether that be M
or S
If use cytoplasm injection experiments, from later stage injected into earlier
cell, mitosis is triggered, has to be a positive signal to trigger it into mitosis –
aka a cyclin protein
3 types of proteins:
1. Cyclins
• Vary in level throughout cell cycle
• Bind & activate cdks
• Necessary but not always sufficient to activate the cdks
2. Cyclin dependent kinases (Cdks)
• Activation depends on cyclin binding + further phosphorylation
3. CAKs – Cdk activating kinases
• Need to be phosphorylated at thr of active site
Variation in cyclin B concentration
Cyclin itself can’t be responsible for entering into mitosis –
not a gradual entry
Cyclin has to reach threshold level before entering into
mitosis, will bind to cdk before MPF becomes active
, MPF
• MPF = mitosis/maturation promoting factor
• MPF is a kinase made up of a complex of cyclin & cdk
• Full activity of MPF is essential for entry into mitosis
• MPF also activates a pathway leading to its own degradation, so it disappears when
its job is done
Cyclin B is not sufficient to send cell into mitosis by itself, will
bind to cdk protein, complex = MPF, once binding = active
MPF, will send cell into mitosis
Active MPF= initiates sequence of events happens in
particular order
1. Nuclear envelope breaks down – enables regulatory
factors to move into nucleus, allows Spindle fibres growing
from poles to enter cells to make contact with kinetochores
2. Chromosomes shorten & thicken
3. Mitosis occurs
How MPF works (acts as a kinase to phosphorylate)
• MPF is a Cdk1 (Cdc2)-cyclin b complex
• It activates numerous proteins by phosphorylation
1. Lamins – causing the nuclear membrane to disperse, layer of proteins that form
undeath nuclear membrane when MPF phosphorylates lamins, structure of mesh
breaks down as does nuclear envelope
2. Condensins – promoting chromosome condensation (also cohesisns)
3. Histone H1 – Promoting chromatin condensation, 4 histones makes up protein
optima, linker histone, brings beads on string to a closer formation, so MPF trigger
this causes coiling & bringing together
4. Cdc 25 – a phosphatase that removes P from cdk1-cyclin B complex to fully activate
it
5. APC (anaphase promoting complex) – key role in metaphase → anaphase
checkpoint
Summary
Four main stages of the cell cycle (G1, S, G2, M).
• Three key checkpoints of the cell cycle (G1>S, G2>M, metaphase > anaphase).
• Cyclins and cdks form a complex called the Mitosis Promoting Factor (MPF).
• MPF acts by phosphorylating a number of proteins to allow entry into mitosis (or
meiosis!): lamins, condensins, histone H1, cdc25, APC
Lecture 2
NOTE: PRINT SLIDES 21-30
Notes for slides printed
On right has some activity but low on left highly active sends cell into mitosis
Orange = cyclin B, Blue = Cdk
3 phosphate groups on MPF – how cdc 25 & MPF work
One of phosphate groups activate MPF – one added b the CAK (Cdk activating kinases)
