Cell Replication Flashcards
what is cell cycle?
sequence of events in which a cell duplicates contents and divides into 2
cell will roughly double in size before dividing
how long do embryonic stem cells take to divide?
30 mins
hepatocytes?
1 year
intestinal epithelial cells?
around 20 hrs
which cell type(s) never divide?
neurones and cardiac myocytes
stages of cell cycle?
G1, S, G2, M
what is G0?
a quiescent phase where cells are dormant and not dividing
carries out all cellular functions though
this happens in absence of stimulus
e.g. of G0 cells?
neurons, skeletal muscle, hepatocytes
G1 checkpoint?
before S phase, checks for whether cellular environment is favourable
G2 checkpoint?
is all DNA replicated?
is all DNA damage repaired?
mitosis checkpoint?
are all chromosome properly attached to mitotic spindle?
why/how do cells ever leave G0?
response to growth factors (tell a cell to move from G0 into G1)
signal amplification
signal integration
Ras/Raf/MEK (protooncogenes)
c-Myc?
stimulated by growth factor
c-Myc promotes G0 to G1 transition
=oncogene, overexpressed in many tumours
Cdks?
cyclin dependent kinase
controlled by phosphorylation/ dephosphorlyation
allows exquisite control of events
only active when CYCLIN is bound
which 3 amino acids can be phosphorylated and why?
serine, threonine, tyrosine
they contain -OH group
nomenclature of cyclins?
their concentrations fluctuate within cell cycle
cell cycle entry requirements?
growth factor –> C-Myc –> cyclin D –> cyclin D/Cdk 4/6 complex
protein kinase cascades?
often the protein regulated by a kinase is a kinase and so on… this creates a protein kinase cascade
leads to:
signal amplification
diversification
OPPORTUNITY FOR REGULATION
kinases?
phosphorylate another molecules, e.g. a protein and thereby activating it
phosphatases?
reverses phosphorylation, deactivating a kinase
is expression of cyclins transient or are they present throughout cell cycle?
transient, they’re expressed at specific points in cell cycle
this is in contrast to Cdks which are present throughout cell cycle
how are Cdks regulated?
phosphorylation
interaction with cyclins
steps of Cdk activation
- inactive cdl
- cyclin binds, inactive cyclin-Cdk complex
- an activating protein phosphatase gets rid of the inhibitory phosphates, thereby activating the complex (i.e. sequential phosphorylation and dephosphorylation)
positive feedback?
drives cell cycle forward
how are cyclins turned off?
ubiquitination = method to degrade proteins
in this example we are degrading cyclin, thus inactivating Cdk
sequential?
one Cdk will activate the cyclin which is required for the next phase
e.g. Cdk4/6 stimulates expression of cyclin E
this gives DIRECTION and TIMING to cycle
Rb?
=retinoblastoma (present in all nucleated cells)
a molecular ‘brake’
it’s a tumour suppressor, so when it’s missing/inactive it can cause tumours e.g. a retinal tumour
function of Rb?
acts as a brake on cell proliferation
sequesters a transcription factor in inactive form
the TFs cannot turn on genes needed for cell cycle progression e.g. DNA polymerase, thymidine kinase
how can the brake be released?
activation of intracellular signalling leads to production of G1-Cdk and G1/S-Cdk complexes
these phosphorylate Rb, inducing the inactivation of Rb and release of the TF
target genes such as those which control enzymes such as DNA polymerase and thymidine kinase can now be activated
what specific example of TF?
E2F
release of E2F allows what?
cell cycle progression
p53?
a tumour suppressor
arrests cells with DNA damage in G1
protein kinases phosphorylate p53, activating it
p21 gene
induced by active p53
=another molecular brake
inhibitor of cyclin:Cdk complexes
this makes sense as cyclin:Cdk complexes cause activation of G1 and the cell cycle
examples of oncogenes
EGFR/HER2: over-expressed in breast cancers
Ras: mutationally activated in many cancers
Cyclin D: overexpressed in 50% of breast cancers
C-Myc: overexpressed in many tumours
tumour suppressor examples?
Rb - loss of function mutations in 80% of small cell lung cancers
p53 - loss of function mutations in over 50% of all cancers
what is p21?
cyclin-dependent kinase inhibitor, can inhibit all Cdks
