Week 7 Flashcards
RAS proteins
essential for signaling cells to
divide and grow (proliferate)
- mutated in 30% of human cancers
Mutant Ras protein
stimulates cell growth
and division even when there is no external
EGF binding to EGF-R
(However, microRNA Let-7 can block mutant
RAS)
when RAS RNA binds let-7
no translation by ribosome –> no RAS protein
how do microRNAs control gene expression
by blocking translation
ligand
external signal
lig (bind) as in “ligature”
simple chemical signalling model
external signal (ligand)
membrane receptor
internal signal transduction
internal response
Endocrine signalling
hormones…
gland secretion into blood
Paracrine signalling
chem signal secreted from neighbour cells
Autocrine signalling
chem signal secreted and acting on source cell
ATRA
all-trans retinoic acid
- derived from vitamin A
- binds receptors and activates genes needed for differentiation
steroid hormones
i.e. testosterone
promote growth and cell
division in some tissues
what gene mutations and mutation effects would benefit tumour development
dominant mutations
gain-of-function mutations
mutation that results in an overactive mitogen’
mutation that results in unregulated mitogen
mutation results in excessive mitogen synthesis
phagocytosis
process by which certain living cells called phagocytes ingest or engulf other cells or particles
cytochrome c released from cell
mitochondria into cytoplasm during apoptosis
- stops ATP synthesis, stopping cell metabolism
cytochrome c purpose in normal cell
attached to inner membrane
It transfers electrons to molecules
(respiratory complexes) so they can
move protons needed for ATP
synthesis.
BAX
pro-apoptosis gene / “tumour suppressor” proteins
causes opening of outer membrane when activated
caspases
proteins activated when cytochrome c is released
clusters of large vesicles during apoptosis
degrading cytoplasm contents include protein
fragments
If inhaled radon-222 gas
decays in lungs radioactive polonium metal is deposited.
- Radioactive polonium and other metallic
decay products remain in lungs emitting
alpha or beta particles until non-radioactive
lead is produced.
Rob McIntosh
healthy and fit 31-year-old
non-smoker diagnosed with metastatic lung
cancer (p. 37, Sidebar 2.3), and died at 33.
- believed radon in family home cause
bcl2
production in larger amounts may keep cancer cells from dying
(survival signals)
successful cancer cell
unregulated ability to grow and divide
no/only partial differentiation
- mitogens : abundant, overactive, unregulated
- antimitogens : suppressed
increased mutation rate
Proto-oncogenes
activating, dominant,
gain of function mutations, increased
expression, affecting Bcl2 for example
cell fate determination is regulated by…
chemical signalling (internally and externally)
Cell fates
1: survive
2: Grow and divide
3: differentiate
4: die
oncogenic mutations cause…
unregulated gene expression
synthesis of unregulated and/or overactive proteins
phagocytes
immune system cells that can surround and kill microbes and remove dead cells
proteases
aka proteinases
- destroy cell proteins
- activated by CC release
more specifically : caspases
tumour suppressor proteins
pro-apoptotic molecules (anti-mitogen)
ex. BAX
all cell survival signals
are proto-oncoproteins
universal cell survival genes
proto-oncogenes (grow and divide)
tumor-suppressor genes (pro-apoptosis)
tumour-suppressor genes (differentiation)
successful cancer cell
like a stem cell
unregulated ability to grow and divide
no/partial differentiation
no apoptosis!
