The Cell Cyle and Signalling Flashcards
what is the definition of the cell cycle?
the interval between 2 successive mitosis divisions resulting in the production of 2 daughter cells with identical chromosomes
what are the 4 main phases of the cell cycle?
G1, S, G2 and M
what stages of the cell cycle make up interphase?
G1, S and G2
what is G0? how do cells exit G0?
- cells are no actively dividing -> quiescence
* external signal (eg. APC) or mitogenic factor
describe G1 (4)
1 - cells enter G1 after stimulation by a growth factor
2 - RNA and proteins are synthesised in preparation for S phase
3 - growth in size
4 - restriction point, after which the cell is committed to division
describe S phase (2)
1 - DNA is synthesised to make 2 copies of chromosome
2 - intra-S checkpoint with p53 which checks for DNA defects
describe G2 (2)
1 - organelles replicated in preparation for mitosis
2 - further growth (double in size since start of G1)
describe prophase (4)
1 - chromatin condenses
2 - nucleolus + nuclear membrane disappear
3 - centrosomes move to opposite poles
4 - chromosomes attach to microtubules
describe metaphase (1)
1 - spindle fibres align chromosomes along middle of nucleus
describe anaphase (2)
1 - proteolytic cleavage of centromere
2 - sister chromatids separate and move to opposite sides of the cell
describe telophase (3)
1 - new membranes form around daughter nuclei
2 - chromosomes condense
3 - spindle fibres disperse
what group of proteins regulate progression through the cell cycle? what action do they perform?
- cyclin-dependent kinases
* phosphorylate serine and threonine amino acids on target proteins
what are cyclins?
small activator proteins whose concentration varies throughout the cell cycle (constantly synthesised and broken down)
describe how CDK1 (aka Maturation Promoting Factor) is activated (5)
1 - cyclin B is transcribed and accumulates during G1
2 - when a threshold amount is reached, CDK1 proteins are activated
3 - inactive CDK1 loses its net phosphorylation to form a complex with cyclin B
4 - permits the cell to enter mitosis
5 - cyclin B is degraded to prevent further CDK activity
what are the 2 ways that CKIs work?
- CDK inhibitor
- inactivate CDK-cyclin complex
- act as competitive inhibitor
what actions does active CDK1 perform to start mitosis? (3)
- phosphorylates nuclear lamins (n.envelope disassembles)
- phosphorylates condensins + histones causing chromosome condensation
- phosphorylates microtubule-associated proteins to allow spindle formation
what conditions are monitored by the cell to regulate the cell cycle?
- favourable external environment - presence of growth factor
- favourable internal environment - sufficient cell growth
- DNA damage
- replication errors
- spindle attachment
- chromosome integrity
where in the cell cycle is the restriction point? what conditions does it check for?
- end of G1
* cell size + favourable external conditions with growth factor
describe how a cell passes the restriction point (5)
1 - retinoblastoma (Rb) inhibits the transcription factor E2F, therefore preventing proteins required for S phase from being synthesised
2 - growth factor is detected on cell surface -> Rays signalling pathway
3 - cyclin D synthesised and accumulates, complexes with CDK 4 and 6 forming activated kinases
4 - Rb is phosphorylated, therefore E2F is uninhibited
5 - S phase proteins synthesised allowing cycle to continue
where are the 2 DNA damage checkpoints in the cell cycle? why are each of them important?
- late G1: check DNA before it is replicated
* G2: check DNA before it is passed to daughter cells
what are 3 causes of DNA damage?
- chemical mutagens
- radiation
- replication errors
what molecule detects DNA damage at checkpoints?
p53
what actions does p53 perform to stop a cell’s progression through the cell cycle? (3)
- signals production of p21 - a CKI to inhibit CDK-cyclin complexes for the next phase (either S or M)
- halts cell cycle to allow for DNA repair (low cellular stress)
- promotes apoptosis (high cellular stress)
what happens at the spindle checkpoint in the cell cycle?
anaphase promoting complex is inhibited until all chromosomes are attached to spindle
what are proto-oncogenes? (2)
- encode proteins involved in regulation of cell growth and mutation
- when mutated, proto-oncogenes become oncogenes which are always active and initiate / speed up proliferation
what are 3 types of oncogenes? give examples of each
- cell surface receptors: amplify signals (HER2)
- transducers: activate enzyme cascades inappropriately (Ki-Ras)
- protein synthesis: accumulation of cell cycle regulators (cyclin D amplification)
what 4 types of mutation can lead to a proto-oncogene to become an oncogene? what effect does each of the mutations have on the protein?
- deletion / point mutations - hyperactive protein made in normal amounts
- regulatory mutation - normal protein is overproduced
- gene amplification - greatly overproduced
- chromosome rearrangement - hyperactivity or overproduction
what is the role of tumour suppressors?
- maintain integrity of the genome
- cause cell cycle arrest in abnormally dividing cells
- or repair DNA damage
give 3 examples of tumour suppressors
- Rb - blocks entry to cell cycle
- p53 - detects DNA damage to haunt cell cycle
- BRACA1 - repaired DNA (mutated in may types of breast and ovarian cancers)
why are most tumour suppressors described as requiring ‘two hits’? what important tumour suppressor does this not apply to?
- both alleles of the protein must be mutated for the protein to be inhibited as a tumour suppressor
- p53 is made up of 4 polypeptide chains, ie. shape of overall protein will mostly be affected even if only one allele is mutated
what are the 3 broad signal types in the body?
- physical - response to sensation
- electrical - impulses
- chemical - hormones, growth factors, neurotransmitters
what are the 4 types of hormones based on chemical structure? give examples of each
- amine - amino acids with a modified group (noradrenaline)
- peptide - short amino acid chains (oxytocin)
- protein - long peptide chains (human growth hormone)
- steroid - derived from lipid cholesterol (oestrogen, testosterone)
what are the 4 ranges of action for hormones?
- endocrine - long distance, via blood
- paracrine - short distance, via diffusion
- juxtacrine - neighbouring cells, via cell:cell contact
- autocrine - same cell
describe how hydrophobic signals work (4)
(eg. steroid hormones)
1 - diffuse through phospholipid membrane
2 - bind to intracellular receptors
3 - hormone-receptor complex acts as a transcription factor
4 - binds to DNA to alter gene expression
what are 3 types of cell surface receptors? give examples of chemicals using these receptors
- ion channel linked - ions flow into cell to change charge (glutamate neurotransmitter)
- G-protein coupled (GPCR) - signal activates a G-protein which passes the signal into the cell (adrenaline)
- enzyme linked - either via dimerisation or through direct activation of enzyme (receptor tyrosine kinases - growth factors)
what is the definition of transduction?
relay system that takes signal to a specific place to trigger a specific response, may also amplify signals
what are the 2 main types of transduction
- enzyme cascade
* secondary messengers
what type of transduction is the MAPK/Ras pathway? describe the MAPK/Ras pathway - activation order (6)
• enzyme cascade
1 - EGF binds to and activates the tyrosine kinase receptor EGFR
2 - active EGFR activates SOS
3 - SOS activates K-Ras
4 - K-Ras activates MAP3K
5 - MAP3K activates MAP2K, which activates MAPK (amplification step)
6 - MAPK activates Myc, a transcription factor that synthesises proteins in response to the signal
what is the basic principal of secondary messengers?
small proteins produced in large quantities after receptor activation which then go on to actives several different proteins
what is the structure of a G-protein coupled receptor?
7-span transmembrane structure
what are 3 important signalling molecules that use GPCRs?
adrenaline, rhodopsin, glutamate
what are the subunits of a G protein?
alpha, beta and gamma
describe how a G protein is activated by an activated GPCR (4)
1 - G protein binds to activated receptor
2 - receptor promotes exchange of GDP for GTP (inactive to active state)
3 - when activated, G protein separates into 2 effectors - alpha unit + GTP and beta + gamma
4 - signal turned off by GAP/RGS -> cause GTP to hydrolyse and return G to heterotrimeric state
describe the signalling pathway of adrenaline in increased blood glucose (6)
1 - adrenaline activates GPCR
2 - triggers activation of G protein -> alpha unit activation
3 - alpha unit activates adenylyl cyclase which produces the secondary messenger cAMP
4 - cAMP activates Protein Kinase A (PKA)
5 - PKA has 2 actions:
• phosphorylate and activate phosphorylase kinase
• phosphorylate and inhibit glycogen synthase
6 - phosphorylase catalyses glycogen to glucose, synthase is prevented from catalysing glucose to glycogen (glucose release)
describe how the adrenaline signal is switched off (3)
1 - adrenaline detaches and GPCR inactivates
2 - G protein inactivated so cAMP production is inhibited
3 - phosphodiesterases breakdown remaining cAMP
what are the effects that adrenaline produces in different tissues (5)
- cardiac muscle: increase heart rate and force
- airway smooth muscle: bronchodilation
- BV of skeletal muscle: vasodilation
- BV of peripheral organs: vasoconstriction
- adipose tissue + liver: glycogenolysis
what are the 4 ways that tissue specificity can be achieved for a single signalling molecule?
- different GPCR to trigger different effects
- different G protein
- different effectors / trigger different events in effector
- different secondary messengers that have different targets
what are the 2 ways that an action potential can be started?
- stimuli activates Na+ channels directly
* neurotransmitters binds to receptor and causes ion movement to trigger action potential
what is summation? where does it occur in the axon?
- both excitatory and inhibitory inputs are added together -> if the threshold potential is reached after adding together, then AP is triggered
- axon hillock (beginning of axon just after cell body)
what is the different between spatial and temporal summation?
- spatial summation - inputs arise from different dendrites
* temporal summation - not enough time to reach resting potential between inputs (excitatory)
what are the main chemical types of neurotransmitters? give examples (4)
- amino acids + derivatives: glutamate (main excitatory in CNS), GABA (main inhibitory in CNS)
- catecholamines (monoamines) derived from tyrosine: dopamine and serotonin
- acetylcholine derived from choline (important at neuromuscular junction)
- peptides: substance P and endorphins
