Control of Cell Proliferation Flashcards

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1
Q

Cell numbers must be controlled:

Control involves ….. ………….., …….. …….. ……… and …………. ………..

A

cell communication

cell-cell contacts, growth factor signals

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2
Q

What is the cell cycle?
What does it involve?
Why is important?

A
  • the processes of growth and division
  • involves checkpoints and feedback control
  • important for maintenance of genome integrity
    and symmetrical cell division
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3
Q

What are the 4 phases of the cell cycle?

A

G1 - growth, preparation for DNA replication
S - replication of DNA
G2 - growth,
M - mitosis

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4
Q

What are G1, S and G2 collectively known as?

A

interphase

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5
Q

Define a checkpoint

A

A critical control point in the cell cycle where stop and go-ahead signals regulate the cell cycle

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6
Q

In what phases do they 3 prominent checkpoints take place?

A

G1 checkpoint
G2 checkpoint
Metaphase checkpoint

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7
Q

Describe the G1 checkpoint.
What is it checking for?
How does it do this?

A

The Restriction Point

  • ensures cell is large enough to divide
  • if receives go ahead, will continue with cell cycle
  • if no signal, it will exit the cycle and switch to G0 (a non dividing state)
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8
Q

Which phase are most cells in the human body in?

A

G0 i.e. a non dividing state

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9
Q

Describe the G2 checkpoint

A

ensures that DNA replication in S phase has been completed successfully

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10
Q

Describe the metaphase checkpoint

A

ensures that all of the chromosomes are attached to the mitotic spindle by a kinetochore

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11
Q

Which enzymes regulate the cell cycle?

How?

A

cyclin dependent kinases

fluctuations in the abundance and activity of cyclins and CDK’s pace the events of cell cycle

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12
Q

What is a kinase?

Where do they act in the cell cycle?

A

An enzyme which activates of deactivates a protein by phosphorylating it
Kinases give the go-ahead single at the G1 and G2 checkpoint

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13
Q

How are CDK’s activated?

A

cyclins accumulate during the G1, S and G2 phases of the cell cycle, binds to CDK’s

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14
Q

What does mCDK regulate and how?

A

Regulates mitosis
Enough cyclins available by the G2 checkpoint to form complexes which initiate mitosis (by phosphorylating key proteins in the mitotic sequence)
Later in mitosis, mCDK switched off by initiating a process that destroys cyclin
New cyclin is synthesised during the next interphase

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15
Q

What role does pRB have in the cell cycle?

A

Retinoblastoma protein
Regulates G1 checkpoint
In the absence of GF’s pRB binds to transcription regulators of genes for cell proliferation, prevent continuation of the cell cycle
Growth factors large surface receptors activating CDK’s which phosphorylate pRB, causing it to release its binding of transcription factor regulators. These activate genes for cell proliferation

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16
Q

True or False?

pRB is a tumour supressor gene

A

TRUE - pRB is a tumour supressor gene, if mutated it may cause uncontrolled cell division

17
Q

What role does p53 have in the cell cycle?

A

Acts at G1/S checkpoint
DNA damage causes an increase in protein p53 which activates the transcription of protein p21, an inhibitor of CDK , so preventing continuation into S phase, giving time for DNA repair
If DNA damage is too severe, p53 can induce the cell to apoptose

18
Q

What are the consequences of checkpoint failure?

A
  • proliferation of cells in the absence of growth factors
  • repliaction of damaged DNA
  • segregation of incompletely replicated chromosomes
  • division of cells with wrong number of chromosomes
19
Q

What is angiogenesis?

A

Formation of new blood vessels

20
Q

Describe a normal growth factor signalling pathway

A
Signal binds to receptor 
RAS protein (GPCR)
Kinase cascade 
Gene regulatory proteins 
Expression of genes required for proliferation
21
Q

What 3 aspects of the growth factor signalling pathway can become oncogenic? Give examples

A

Receptor - mutated, constitutively active, or over-expressed (e.g. Her2 in breast cancer)
Signalling proteins - mutated, constitutively active Ras protein
Regulatory protein levels - over expression of myc (TF) can cause deregulated cell proliferation