10-23: Cell cycle control and cell division Flashcards
Cell cycle control
- DNA replication to 2 identical daughter cells
- 3 major checkpoints
- many of the genes (proteins) involved in cell cycle regulation are critical determinants of cancer progression
Interphase
G1: growth and metabolic
S: replication of DNA
G2: growth and prep
Mitosis
P: condensed
M: center
A: segregate
T: decondensed
Cytokinesis
Cell splits (two identical daughter cells)
Resting Phase
G0
G1/S Checkpoint
Check for:
Nutrients
Growth factors
DNA damage
G2/M Checkpoint
Check for:
cell size
DNA replication
Metaphase to anaphase checkpoint
Check for chromosome spindle attachment
Cell cycle checkpoint control system
- Dependant on cyclically activated cyclin dependant protein kinases (Cdks)
- dependant on cyclical proteolytic events
- dependant on transcriptional regulation
Cell cycle checkpoint control system
- Initiates/ends events
- proper order and fidelity
- Intracellular and extracellular dependant
- Arrests the cycle (fails to complete a process or unfavorable conditions)
cyclins and cyclin dependant protein kinases
- Cdk binds to cyclin
- phosphorylation
- active cyclin Cdk complex
Cyclin D
Cyclin D
Cyclin E
G1/S cyclin
Cyclin A
S cyclin
Cyclin B
M cyclin
The concentrations of cyclins _____________ while Cdk ________________.
The concentrations of cyclins CHANGE while Cdk DO NOT CHANGE.
Anaphase-promoting complex (cytosome)
APC/C: initiates the metaphase to anaphase transition
What happens to expose the active site on CDK?
- Cyclin binds to cdk
- Opens up the T loop (Partial active)
- T loop is phosphorylated, fully active (fully active)
The activity of cyclin-cdk is further regulated by
WEE 1 kinase= phos Cdk at different site= INACTIVE
Cdc25 phosphatase= removes the wee phos= ACTIVE
Proteolysis
protein degradation
What family of proteins is the anaphase-promoting complex?
ubiquitin ligase
Function of APC/C
trigger metaphase -> anaphase by tagging specific proteins for degradation
What does APC/C catalyze?
ubiquitylation and degradation of securin and the S and M cyclins
When is APC/C active?
Mid mitosis and remains active in G1
Control of cell cycle through APC/C
Cdc 20 activates APC/C -> ubiquitinizes m-cyclin
SCF
Skp1, cullins, F-box proteins
What family of proteins is SCF?
Ubiquitin ligase
Function of SCF
Ubiquitylates Cdk inhibitor (CKI) proteins in LATE G1 (like p27)
Control of proteolysis by SCF
- SCF binds to F box protein = active
- Ubiquitinizes Cdk inhibitor protein
- Cdk inhibitor is degraded in proteasome
- Control by transcription
Cyclin gene expression is regulated and specific cyclin genes are turned on
G0
- lack of growth factors/nutrients
- term diff: (heart muscles, nerve cells, bone osteocytes)