Lecture 20 - controlling proliferation & differentiation Flashcards
what does EPO do
erythropoietin
a secreted cytokine that stimulates RBC production via changing gene expression
what tissues are highly proliferative
skin
intenstine
name of area of the stem cells in the intestine
crypt
name of phase that cells go into if they dont wanna proliferate anymore
quiescence
stay stuck in G1
what type of cells usually stay in quiescence
highly specialised ones
e.g. cardio myocytes
neurons
name of disease that means over proliferations
hyperplasia
name of factors that stimulate proliferation and stimulate growth
prolif = mitogens
growth = growth factors
example of inhibition of proliferation
myostatin
activates pathways that stim production of CKIs
which inhibit active cdk cyc complexes from forming
what is the restriction point
in G1 phase where if it passes this poing hten proliferation cant be stopped
before this, cells are responsive to growth and prolif factors
how do mitogens induce expression of cyc D
mitogen triggers receptor tyrosine kinase
which triggers Ras GTPase
which triggers MAP kinase pathway
which triggers transc factors
which forms cyclin D
what happens once cyc D is formed
binds with CDK 4/6
what does active cycD/CDK4/6 phosphorylate
Rb
which then releases E2F which becomes active
and now this allows transcription for cyclin E
how is the production of Cyclin E powered by +ve feedback
- CDK2 (the one that binds with cyclin E) can also phosphorylate Rb, so it drives its own synthesis
- E2F can also stimulate synth of more E2F
what are Wnt signals and what secretes them
paneth cells secrete Wnt signals
which trigger cell proliferation in stem cells
how do stem cells know when to stop proliferating
they migrate upwards and away from the base area which is where the Wnt signals are being released
so they stop proliferating