WEEK 2 Flashcards
What is cell proliferation?
the process by which a cell grows and divides to produce two daughter cells, leads to exponential increase in cell number
What is the fundamental basis of cell proliferation?
New cells must be identical therefore growth and division process (cell cycle) must be tightly controlled
How is the cell cycle controlled?
Checkpoints and feedback control
Give the stages of the cell cycle
G1 phase->growth and preparation for DNA replication
S (synthesis) phase->DNA replication
G2 phase->growth and preparation for mitosis
M (mitosis) phase->chromosome segregation, cell division, cytokinesis
What is cytokinesis?
Cytoplasmic division after mitosis, forming 2 daughter cells with similar amount of nuclear DNA and organelles
What are cell cycle checkpoints?
Critical control points where stop and go-ahead signals can regulate the cell cycle
What are the three major checkpoints?
G1, G2 and M checkpoints
Describe the G1 checkpoint (restriction point)
ensures cell is large enough and contains enough nutrients to divide. if cell doesn’t receive go-ahead signal at this point, it will exit the cell cycle and switch to a non-dividing state (G0)
Describe the G2 checkpoint
ensures DNA replication in S phase is completed successfully
Describe the Metaphase checkpoint
ensures all chromosomes are attached to mitotic spindle by a kinetochore
What occurs if there’s failure at any of these checkpoints?
Apoptosis-induced cell death
What enzymes regulate the cell cycle?
Cyclin-dependent kinases (CDKs)-G1, G2 and M CDKs
How are CDKs activated?
Phosphorylation due to Cyclin binding-a molecule which’s fluctuations indicate a need for new cells in a specific area
How do CDKs regulate the cell cycle?
They activate and encourage the continuation of the cell cycle to proliferation
What is a kinase?
A protein which activates or deactivates another protein by phosphorylating them
When do cyclins accumulate and what effect does this have on mitosis?
During G1, S and G2 phases, leading to enough cyclin available by the end of G2 checkpoint to form M-CDK complexes initiating mitosis
How does M-CDK switch itself off?
Initiating a process which leads to cyclin destruction
Which cyclin-CDKs are required at the restriction point?
CDK4/cyclin D and CDK2/cyclin E/A
Which cyclin-CDKs are required at the Metaphase checkpoint?
CDK1/cyclin A/B
What regulates the restriction point?
Retinoblastoma protein (pRB) which is a tumour suppressor protein
How does pRB regulate the restriction point?
In absence of growth factors, pRB binds to transcription regulators of genes for cell proliferation, preventing cell cycle continuation
Growth factor presence causes activation of G1 and G1/S CDKs which phosphorylate pRB and cause its release from transcription regulators, activating genes for cell proliferation
What regulates the DNA damage checkpoint (G1/S phase)?
p53 which is a tumour suppressor protein
How does p53 regulate the DNA damage checkpoint?
p53 increases due to DNA damage, activating transcription of p21, an inhibitor of CDK, preventing continuation into S phase, giving time for DNA repair
What happens if DNA damage is too severe?
p53 can induce apoptosis
What occurs due to a loss of function mutation?
Unrestrained replication of damaged DNA, leading to genomic instability/resistance to apoptosis
What are the consequences of checkpoint failure?
Proliferation of cells in absence of growth factors, replication of damaged DNA, segregation of incompletely replicated chromosomes, divisions of cells with wrong number of chromosomes->leads to genomic instability and increased rate of mutation
Hallmarks of cancer are
Sustaining proliferative signalling Evading growth suppressors Activating invasion and metastasis Enabling replicative immortality Inducing angiogenesis Resisting apoptosis
Stages of a growth factor signalling pathway
membrane receptor activation leads to dimerisation and phosphorylation, adapter protein binds to phosphorylated receptor in cytoplasm, Ras (G-protein) binds to adaptor, signalling cascade, phosphorylation of gene regulatory proteins, expression of proliferative genes
Define oncogenic
pertaining to the origin or development of tumours or cancer
What is the result of receptor becoming oncogenic?
deregulated cell proliferation due to mutated/constitutively active/over-expressed receptor causing signalling pathway occurrence without presence of growth factor
What is the result of signalling proteins becoming oncogenic?
deregulated cell proliferation without activation of receptor due to mutated/constitutively active Ras/Kinase proteins
What is the result of regulatory proteins becoming oncogenic?
deregulated cell proliferation due to over-expression of transcription factors
LOOK OVER NOTES ON:
Metabolism and its control (1) and Appearance and Classification of Epithelial tissue (+histology)
