Lecture 10 - The cell cycle Flashcards
When does DNA replication occur
before mitosis in the S phase
what does the M phase consist of
both mtosis and cytokinesis
start transition
is the environment favourable?
G2/M transition
is all dna replicated?
is environment favourable?
metaphase to anaphase transition
are all chromosomes attached to the spindle?
checkpoints
ensure conditions are suitable for division
how are checkpoints mediated
by the controlled activity of cyclin-dependent kinases
what do cdks do
they phosphorylate target proteins for the cell cycle to progress
what do cdks require
cyclins
when are cdks present
can be present throughout all cell cycel stages
when do cyclins and cdks work
one cdk may work with multiple cyclins,
degradation of cyclins
cyclins can be ubiquinated
polyubiqtylation marks cycline for degradtion by the proteasome
If cyclins are broken down CDKs will no loner be active
what promotes M cyclin degradation
APC/C and Cdc20
What do APC/C and Cdc20 act as
They act as an E3 ubiquitin ligase
What are CDKs activated by
cyclins (by exposing T loop) and Cdk-Activating kinase (Once T loop is exposed CAK can hosphorylate Cdk to further actuvate it)
what reverses the effect of cyclin cdks
protein phosphatases (PP2A) remove phosphorylation from proteins
thye usually have same targets as cyclin-cdks
what particpates in a complex feedback loop
PP2A and M-CDK participate in a complex feedback loop
what happen before m phase
- PP2A is active
- PP2a desphosphorylates M-CDK targets to stop progession into mitosis
what happens during m-phase
- M cyclin is produced
- M CDK is active
- M Cdk indirectly inhibits PP2A activity
- M cyclin phosphorylates its target to promote mitosis progression
how can cyclin-cdks be inactivated
- cdk inhibitor proteins (CKI) binds cyclin cdks
CKIs disrupt the Cyclin-cdk interaction which inactivates the cdk - phosphorylation
the inhibitory phosphorylation is at a different site from the activating phosphate added by Cak
examples of cdk inhibitor proteins
p27 and p21
Wee 1 kinase
can add an inhibitory phosphorylation
Cdc phosphatase
remove inhibitpry phosphorylation
it must be phosphorylated to be active
positive feedback loop to ensure cyclin-cdk activation
- active m-cdk acivates its activators (Cdc25 phosphorylaton)
- Active M-CDK inhibits its inhibitors- PP2A phosphatase inactivation, Wee 1 kinase phosphorylation
how can cells be retained in G1
Rb inhibition of E2F
E2F is a transcirption factor required for S phase gene expressiin
Rb can be inhibited by phosphorylation
Mitogens
trigger production of cell cycle protein myc
what do mitogens activate and then what do they upregulate
they activate a signaling pathway including RTKs, Ras, and a MAP kinase cascade
these upregulate the epression of Myc
Myc
key transcription factor involvd in cell cycle control
how does myc help with the inhibition of rb
- Myc activates G1 cyclin gene expression
- G1-Cdk phosphorylates Rb
- Phosphorylated Rb releases E2F
- E2F activates expression of S-phase genes
Positive feedbacj through:
1. E2F aactivation
2. G1/S Cdk and S-Cdk phosphorylation of rb
how does DNA damade blobk cells cycle progression via CKI synthesis
- DNA damage induces p53 transcription factor activation
- p53 activates p21 expression
- p21 is a CKI that inhibits G1/S-Cdk and S-Cdk
