Tumour pathology 4 and 5 Flashcards
Describe the outer membrane of a cell?
Bilayer of molecules with lipid end and water soluble end.
Lipid ends in the middle and water soluble on inside and outside.
Describe how a ligand binding to a receptor brings about the start of a signal transduction pathway?
A ligand attaches to the receptor on the outside of cell, changes the shape of the inside part of the receptor.
The changed inside part of the receptor now recruits a molecule.
The messenger molecule can be activated and released and travel to its target in the cytoplasm or nucleus (signal transduction molecules).
Give an example of a signal transduction molecule?
BRAF
How is activation and inhibition of a target molecule achieved?
changing a molecule’s shape
recruiting and adding another molecule (e.g. phosphate group)
What is a transcription factor?
binds segments of DNA called promoters (not the actual gene sequence that’s going to be made into a protein).
Promoters bound to sequence of DNA that may or may not be made into RNA.
Transcription factor can inhibit or more usually activate transcription of the gene by recruitment of enzyme that transcribes DNA into RNA.
What are the regulatory sequences and how are they involved in control of the gene?
They are lots of other DNA sequences- which help control the gene
Describe the cell cycle?
G1 (Gap or Growth phase 1)
-many of cells sit in G1 most of the time
S phase
-synthesis of DNA occurs
G2 (2nd gap or growth phase)
-period of rapid cell growth in preparation for mitosis
M phase- mitotic phase where cell division occurs
What is the restriction point in G1?
In G1 there is a point of no return called the Restriction Point (also known as the Start or G1/S checkpoint) beyond which the cell commits to the cell cycle and no longer needs growth factors.
What is the G2-M checkpoint?
this checkpoint stops the cell cycle if there is DNA damage
Describe how growth factor molecules push cell to the G1 restriction point?
The growth factor molecule (a ligand) binds its specific receptor ( a growth factor receptor) and sets off a signal transduction pathway.
The effect is to push the cell along G1 towards the restriction point.
Lots of molecules affect different things in G1 and push the cell along G1 towards the restriction point.
What is the molecular switch at the restriction point in G1?
Restriction point at molecular level involves phosphorylation of a protein.
If only a few phosphate groups are present, cell stays in G1.
If numerous phosphate groups are present- cell progresses through rest of G1 and through rest of cell cycle
What causes phosphorylation?
there are numerous molecules that actually affect the enzymes that phosphorylate
for e.g. kinases
and other things that inhibit these enzymes and decrease phosphorylation
When is the transcription factor, E2F, bound?
proteins with only a few phosphate groups bind a transcription factor called E2F
so the normal state of this protein is active when it can bind E2F molecules
Why can E2F not be added to molecule with numerous phosphate groups?
When numerous phosphate groups are added to the protein it changes shape and releases the E2F molecules.
Protein is inactive as it cannot bind E2F molecules.
What happens after E2F molecules are released?
The E2F molecules then bind various target DNA regulatory sequences (such as promoters) and the cell cycle goes ahead
Describe the need of growth factors before and after G1 restriction point?
so growth factors push G1 towards the restriction point but are not needed beyond the restriction point
What is the protein that is considered the switch of the restriction point?
retinoblastoma gene product
What does the retinoblastoma gene product act as in its normal, unphosphorylated (active form)?
acts as a tumour suppressor gene as it blocks the cell cycle from going ahead.
Which multiple inputs promote the phosphorylation of the retinoblastoma gene product?
lots of glucose
lots of growth factors
Which inputs promote the inhibition of phosphorylation?
lack of nutrients such as glucose
lack of growth factors
To recap : from growth factor molecule to entering the S phase?
The growth factor m molecule sets off a pathway of molecules which ends up with phosphorylation of the retinoblastoma gene product, and the cell may then enter S phase and go through the cell cycle………
Why do growth factors have two parts to them?
Sometimes cells have inactive growth factor receptors that come together to form the active receptor when the growth factor binds. An example of a part of a receptor that does this is HER-2.
What happens when there is DNA damage?
Damage (for example radiation damage) increases a molecule called p53.
What happens when P53 increases in amount?
blocks (via other molecules) the formation of phosphorylated retinoblastoma gene product. And thus blocks G1 from progressing
