Cell Cycle Flashcards
what is known as stage G0
the quinescent stage
- when the cell isn’t dividing- part of GI
which signal cascades occur during preparation for divisions
JAK/STAT, MAPK, P13K, Src
what do JAK/STAT, MAPK, P13K, Src signaling before division cause
transcription of Cyclin D and CDK 4/6
in order to pass via any checkpoint you need
both cyclins and CDKs
activation of cyclin D occurs especially via
Wnt and MAPK
Activation of cyclin D via Wnt
1) Wnt binds to frizzled
2) APC/axin and GSK3beta (kinase) i complex
3) dishevelled binds to APC- activating APCs inhibition GSKbeta
4) therefore GSKbeta doesn’t phosphorylate Beta-Catedin
5) Beta-Catedin (TF) translocates to the nucleus where it transcribes cyclin D and CDK4/6
activation of cyclin D viaMAPK
- EGF/ mitogen bind to TK
- Trans- Autophosphorylation
- Recruiting Grb2/SOS
- Activated SOS bind to RAS (small GTP) and activates by phosphorylation
- RAS- RAF-MEK-ERK
- ERK= TF
- Produces cyclin D and CDK4/6 produced
role of Cyclin D/ CDK 4/6
transitions the cell to G1 out of G0 and also used at the G1/s checkpoint
only the the concentration of Cyclin D and CDK4/6 reaches a threshold
can the cell cycle progress
what occurs during G1
cell synthesises mRNA and proteins to prepare for organelle and DNA replication
absence of int and p53
will stop cyclin D and CDK4/6 being produced- therefore no cell cycle profression
what causes absence of p53
p21/p27
relationship between cyclins and CDKs
cyclins and CDK (kinase) complex, when cyclins binds to CDK they are change conformational (partially activated). Become fully active by phosphorylation by CAK (CDK activating kinase
what fully activates cyclins and CDK complexes
CAS- CDK activating eznyme
what CDKs and cyclins are produced during G1/S
cyclin D and cyclin E and CDK 4, 6, 2
which pathway used in G1/s
RB/E2F
a) Activated cyclinD and CDK complex causes RB to release E2F
b) E2F can translocate to the nucleus and cause transcription of the next cyclin Cyclin E and CDK2
c) CDk2 and cyclin E complex
when cell damage has occurred and mitosis needs to be stopped
-p21/p27 block the association of cyclin/cdk complexes
they block the phosphorylation of the complexes by blocking CAK (steric hinderence)
e.g. P21/P27 preventing Cyclin D/CDK4/6 from activating RBand therefor eRB/ E2F do not dissociated and E2F cannot translocate to the nucleus and can cause transcription of Cyclin E and CDK2
p53 pathways transcribes
p21/p27
P53 pathway
P53 which transcribed P21/P27
- Activated during DNA damage
a) During cell damage ATM kinase activated
b) This phosphorylates Chk kinase ½ which causes P53 to dislocates from MDM2
c) P53 transolcates to the nucleus and repairs DNA and also transcribes P21/P27
how to P21 and P27 stop mitosis
e.g. P21/P27 preventing Cyclin D/CDK4/6 from activating RB and therefor eRB/ E2F do not dissociated and E2F cannot translocate to the nucleus and can cause transcription of Cyclin E and CDK2
S1 phase
- Cyclin A resides in the nucleus and associates with CDK2
- When the quantity of cyclinA/CDK2 complex reaches the threshold value it inhibits cyclin E
- This suppresses previous cycles i.e. the cell cycle can progress and not start another cycle
cyclins in S1 phase
cyclin A and CDK 2
G2 phase
Cells checks for faithful replication of DNA
Produces proteins needed for cell division
- Cyclin B complexes with CDK2 (suppressed by p21, p27)
- Cyclin B causes transcription of proteins important in spindle formation e.g. microtubules
cyclins ing G2
cyclin B and CDK2 - transcription of microtubules for spindle formation
G2/M checkpoint
In a normal cell:
a) Wee1 is phosphorylated
b) Meaning it can be tagged with ubiquitin (E1, E2, E3 ubiquitin ligase)
c) Sent to proteasome for degradation
d) Cyclin B then complexes with other proteins which allows transition through G2/M checkpoint
metaphase
- Centrioles migrate to the piles
- Radiate spindle (microtubule)
- Spindle fibre binds to cohesion preventing premature chromosome separation)
what is important in metaphase
that all chromosomes are attached to spindles at the kinetochore
how does the cell check all spindle fibre are bound to the kinetochore
- Spindle fibre binds to cohesion preventing premature chromosome separation
- P31 is released from cohesion when all spindle fibres are bind to kinetochore
- Causing APC to bind to securing/seperase
- Seperase binds to cohesion and allows spindles to contract and pull chromosomes apart
mitochondria
H2O2 inhibits pathways such as
MAPK, P53 stopping initiation of cell cycle
p53 causes the transcription of
p21/ p27
p21/p27
produced due to p53 transcribing them
- stop cell cycle progression by inhibiting CAK
