Cell Replication Flashcards
What is the cell cycle?
Sequence of events where a cell duplicates its contents and divides in two
- duplication
- division
- co-ordination
What causes cells to divide at different rates?
Embryonic vs adult cells
Complexity of system
Necessity for renewal
State of differentiation
Tumour cells?
What are the stages of the cell cycle?
G0
G1
S
G2
What is G0?
Quiescent phase —> cells go there in absence of stimulus
Cells not dormant —> non-dividing
What cell cycle checkpoints are there?
G1 —> damaged DNA, unfavourable extracellular environment
- nutrients
- growth factors
S —> damaged or incompletely replicated DNA
G2 —> damaged or incompletely replicated DNA
M —> chromosome improperly attached to mitosis spindle
How do cells leave G0?
Response to extracellular growth factors\
Growth factor binds to GF receptor on cell-surface
—> initiates intracellular signal pathway
—> increase in protein synthesis + decrease on protein degradation —> cell growth
MAP kinases involved
What is c-Myc?
Transcription factor that promotes G0 to transition to G1 by stimulating the expression of cell cycle genes
Oncogene expressed in many tumours
What are cyclin dependent kinases?
Entities part of key signalling events in the cell cycle
—>Phosphorylation + dephosphorylation at serine, threonine and tyrosine residues
Allow for tight control of the cell cycle
Present in all proliferating cells but only active when cyclin is bound
Where do cyclins get their name from?
Their concentration within the cell fluctuate
—> production + degradation
What events need to happen for a cell to move from G0 to G1?
Growth factor bonds to its receptor —> causes c-Myc expression
—> Induces expression of cyclin D —> binds to Cdk 4/6
—> moves cell into G1
What is a protein kinase cascade?
Frequently the protein regulated by a kinase is another kinase
Leads to —> signal amplification
—> diversification
—> opportunity fo regulation
What is the Cyclin-dependent kinases relevance to the cell cycle?
Present in all proliferating cells throughout the cycle
Activity regulated by:
—> interaction with cyclins
—> phosphorylation
What is the cyclins relevance in the cell cycle?
Transiently expressed at specific points ion the cell cycle
Regulated at level of expression
Synthesised, then degraded
Stages of Cdk activation
- Inactive Cdk
- Cyclin binds to Cdk —> cyclin:Cdk complex still inactive
- Protein kinases phosphorylate Cdk at various sites
- Activating protein phosphatase removes the inhibitory phosphate —> activates the complex
How does positive feedback work in Cdk activation?
Once M-Cdk activated —> phosphorylatesCdc25 phosphatase
(now active) —> activates production of more M-Cdk
Helps drive cell from G2 to M phase rapidly
How are cyclins turned off?
By ubiqutination
Ubiquitin molecules are stuck onto proteins that the cell wants to degrade by proteasome cell machinery
How is direction and timing given to the cell cycle?
Cdk become sequentially active and stimulate synthesis of genes required for next phase
Cyclins susceptible to degradation —> hence cyclical activation
What is retinoblastoma?
Protein that is a molecular break
Tumour suppressor
—> if missing or inactive —> issues with cell cycle progression
Abundant in all uncleared cells
What does retinoblastoma do?
Active Rb sequesters a TF in an inactive form
—> TF cannot turn on genes needed for cell cycle progression
—> can’t bind to DNA and induce transcription (e.g DNA polymerase)
What do mitogens do?
Activation of intracellular signalling through mitogens leads to production of G1-Cdk and G1/S-Cdk complexes
—> phosphorylate Rb inducing its inactivation
—> release TF
—> target genes such as DNA polymerase now
activated
What is p53?
Arrests cells with damaged DNA in G1
Regularly being turned over which is why stabilisation is needed
How does p53 work?
Recognises breaks in double stranded DNA
Induces the p21 gene which inhibit cyclin:Cdk complexes by binding them and sequestering them
Oncogene: EGFR/HER2
Mutationally activated or over expressed in breast cancers
Herceptin antibody for the treatment of HER2+ metastatic breast cancers
Oncogene: Ras
Mutationally activated in many cancers
