week 9 Flashcards
Why is correct regulation of cell division important?
Development - Organs and body parts need to be the correct size/shape, not over/under developed.
Injury - Cells need to divide following injury but stop when damage repaired
Adaptive responses
What is adaptive responses regulation important in cell division?
Cells in bone marrow responds to low O2 - produce more RBC - need to stop when O2 returns to normal
Lymphocytes - division triggered in response to antigen - needs to be controlled
What are the consequences of deregulated cell division?
If regulation of cell division breaks down in any of the aforementioned processes it results in cancer/tumor formation
What two main ways cell division is regulated?
External signals - Diffusable chemical signals produced by other cells which ‘tell the cell how to behave’, eg mitogens (growth factors)
Internal signals - chemical signals produced internally by the cell in order to regulate its own division - eg cyclin dependent kinases
External signals regulating cell cycle processing?
Can promote or inhibit cell division,
and are known as Mitogens (growth factors) or anti-mitogens
What happens in the absence of mitogens in external signals that regulate cell cycle?
S phase cyclins (i.e. those cyclins which drive the cell into S phase) are not made
Without sustained mitogen stimulation cells will not progress through the G1 checkpoint
The cells enter G0 instead – quiet phase or quiescence
How do mitogens promote cell growth?
Mitogen binds to specific receptor on plasma membrane - activates - a relay in signal transduction pathway within the cytoplasm - activation of a cellular response as a result
Give an example of an external growth factor?
Platelet-derived growth factor (PDGF)
- Platelets are specialised cells present in blood
- Platelets have important roles in blood clotting and wound healing
- Release PDGF in response to injury
- PDGF binds to receptors on surface of skin cells and causes them to start dividing
What are internal signals that regulate cell cycle?
Stimulated by the presence of extracellular factors such as mitogens
M+G2
M+G1 or S
G1+S
G1+G2
How were internal signals of cell division first identified?
First identified by fusing cells from different stages of the cell cycle, caused the non-mitotic cell to become mitotic due to a growth factor in the cell
Why do cells need internal signals to control division?
Uncontrolled cell division is a hallmark of cancer. So, checkpoints enable cells to stop dividing if the correct signals are not present.
What do checkpoints allow for in cell division (internal signals)?
Checkpoints allow cells to review current circumstances and prevent untimely exit from each cell cycle phase.
If cell proceeds from one phase of the cycle to the next inappropriately, this can cause genetic instability.
Genetic instability can cause cancer
What are the three major checkpoints in cell division?
G1,
G2,
Metaphase (spindle assembly checkpoint)
What does G1 checkpoint ensure?
Commits cell to DNA replication and cell division
Checks:
Is cell suitable size?
Has it received appropriate external signals?
If no, cell enters non-dividing G0 phase,
If yes, Cell proceeds to S phase
What does G2 checkpoint ensure?
Cell makes decision whether or not to enter mitosis
Checks:
Is cell a suitable size?
Is DNA replicated?
Is environment favourable?
NO – cell does not proceed
YES – cell proceeds to M phase
What does metaphase checkpoint ensure?
Occurs in metaphase
Checks:
Are all the chromosomes attached to spindles?
NO – cell does not proceed
YES – cell enters anaphase of mitosis
What are the two internal molecular signals that regulate G1 and G2 checkpoints?
Cyclin-dependent kinases (Cdks) and Cyclins
Who discovered Cyclins?
Sir Tim Hunt (1982)
What did Sir Tim Hunt observe (internal signals of cell cycle)?
Observed that, following fertilisation, cells in sea urchin early embryos divided SYNCHRONOUSLY
Whole population of cells at same stage of cell cycle as opposed to a mixed population at different stages
What did Sir Tim Hunt find (internal signals of cell cycle)?
Found a group of proteins levels of which increased and decreased (cycled) between INTERPHASE and MITOTIC PHASE - CYCLINS
What is the basic mechanism of action of Cdk and cyclin proteins?
Combination of the two proteins known as a ‘promoting factor’ - control progression of the cell into the next phase of the cell cycle
G1 checkpoint – S phase promoting factor (SPF)
G2 checkpoint – M phase promoting factor (MPF) / Maturation promoting factor
How does the G1 checkpoint move to the next phase?
Cyclin E and Cdk 2 phosphorylates proteins required for S-phase entry, drives the cell into S phase.
What regulates G1 and G2 checkpoint?
G1 = SPF
G2 = MPF
How does cyclin enable cells to pass to the next phase of cell division after checkpoints?
Expression levels of Cdk’s remain constant throughout the cell cycle but their activity is enhanced by changes in cyclin levels
therefore, it is an increase in cyclin expression which enables cells to pass through cell cycle checkpoints