Cell replication Flashcards
Which cells in the human body never divide?
cardiac myocytes + neurons
What are the steps of cell replication?
Interphase (G1, S, G2) then mitosis (prophase, metaphase, anaphase, telophase, cytokinesis)
What is G0 phase?
G naught = quiescent phase, without a stimulus, cells go into G0 after G1, instead of S phase
Cells remain busy, not dormant
What does the cell monitor in the external environment before going into DNA replication, during G1 phase?
nutrients & growth factors
What will the cell do if it detects DNA damage?
pause and repair DNA or undergo apoptosis
How do cells leave G0?
tyrosine kinase receptors (growth factors bind to gf receptors) and signal different pathways- increase protein synthesis & protein degradation decreased leading to cell growth (double in size)
growth factor signaling pathway leads to the expression of c-Myc which promotes cyclin expression and hence the activation of Cdks so that: G0 -> G1 then S, etc
What is c-Myc?
transcription factor that stimulates the expression of cell cycle genes
oncogene = overexpressed in many tumours
What are the amino acid residues on kinases (incl. cyclin dependent kinases?)
Serine/Threonine/Tyrosine
-all have OH groups that could be phosphorylated
Where are Cdks present and when are they activated?
present in all proliferating cells, only active once cyclins bind to them and after sequential phosphorylation (2x) by activating kinases & dephosphorylation (1x) by activating phosphatase
What happens to the cyclin concentration within the cell during the cell cycle?
concentration fluctuates throughout, it is cyclic = produced & degraded, it reaches a peak during mitosis and rises steadily during interphase
cyclical activation
What checkpoint exists during S phase and G2 phase?
damaged or incompletely replicated DNA
What checkpoint exists during mitosis phase?
chromosome improperly attached to mitotic spindle
How do protein cascades work in the cell cycle?
One kinase gets activated through phosphorylation and then activates another kinase by phosphorylation again and so forth
What do kinase cascades in the cell cycle lead to?
signal amplification as one kinase can start a cascade w/ many more kinases, diversification as gives the options of different pathways,
opportunity for regulation
What are the names of the Cdks?
Cdk1, Cdk2, Cdk4, Cdk6
What are the names of cyclins?
Cyclin A, Cyclin B, Cyclin D, Cyclin E
Why is sequential phosphorylation and dephosphorylation in activation of Cdks important in the cell cycle?
to avoid abhorrent cell cycling, it’s multiple steps each provide a step that can be regulated
How does positive feedback drive the cell cycle forward?
example with M-Cdk:
active M-Cdk signals the activation of inactive phosphatase (needed to activate more M-Cdk by dephosphorylation) and signal for Cdk-inhibitory kinase which is needed in phosphorylation of the inactive M-Cdk too.
= explosive increase in M-Cdk to drive the cell rapidly from G2 to M phase
What inactivates (turns off) cyclins?
Ubiqutination (cellular post it notes)
= placing a marker onto the cyclin that signals for its destruction
-> cyclin then gets destroyed
Why do Cdks become sequentially active?
stimulate synthesis of specific genes that are required for the next phase = direction & timing to the cycle
What is retinoblastoma protein (Rb) & what is its mechanism?
tumour supressor, “molecular brake”
found in all nucleated cells
mechanism: active Rb binds to transcription factor and keeps it in the inactive form
What happens when Rb is missing or inactive?
cell cycle progresses when it shouldn’t = tumour
eg. children’s eye tumour
How do cells inhibit Rb if the cell is going to proliferate?
Cdks phosphorylate Rb, Rb->inactivated & activated TF is now free to act on target genes
What are E2F family members?
transcription factors that regulate the expression of several genes needed for cell cycle progression (protooncogenes-incl c-myc, cell cycle - incl. cyclins & cdks, & DNA synthesis - incl. DNA polymerase, thymidine kinase)
Which tumour supressor molecule detects damaged DNA in G1 phase and how?
p53
when DNA damaged, will activate protein kinases which phosphorylate p53 -> activated & stable p53 -> binds to regulatory site of p21 gene which undergoes transcription & translation
-> p21 family membranes -> cyclin: Cdk complex inhibited
What happens to p53 in the absence of DNA damage?
degraded in proteasomes
What is EGFR/HER2?
(epidermal growth factor receptor)
oncogene that is mutationally activated or overexpressed in breast cancers
What is a treatment for HER2+ metastatic breast cancer?
Herceptin antibody that blocks HER2+ signaling
What is Ras?
oncogene mutationally activated in many cancers
What is Cyclin D1?
oncogene overexpressed in 50% breast cancers, cells cycle when shouldn’t be
