cours 8 - Cell Cycle II: Extracellular Control Flashcards
What determines the total cell mass?
The number of cell (cell division vs cell death) and cell growth (size)
Total cell mass depends on extracellular factors. What are they?
1.Growth Factors:
- ↑ synthesis
- ↓ degradation of proteins
- Mitogens:
* ↑ cell division - Survival Factors:
* ↓ apoptosis
Give 3 exxemple of growth factors
- platelet-derived growth factor (PDGF),
- epidermal growth factor (EGF),
- nerve growth factor (NGF).
Growth factors act through wich receptors? describe it’s
receptor tyrosine kinase (“enzyme-linked receptors”).
They have 2 domaine that have intrinsic activity, meaning they autophosphorilate.
Describe the cellular pathway of a nerve growth factor signal
- extracellular signal molecule dimer (NGF) binds to TrkA receptor (Tyrosine kinase) (both fins in neurons obviously)
- the 2 domaines come closer together because of membrane fluidity
- they autophosphorylate using ATP
- recruitement of PI-3 kinase that becomes activated
- PI3 kinase phosphorylate PIP2 (a membrane phospholipide)
- That phosphorylate TOR that will activate S6K (they are both protein kinase)
- S6K Phosphorylate ribosomal protein S6 leading to the translation of many important proteins.
Who is Rita Levi-Montalcini and why she should be your idole?
Since females where not permitted ttto do science at this level, she was like: FK it, imma make my own lab in my basement. She removed neurons from mice and isolated sarcoma tissu and discovered neurotrophins (nerve growth factors). She received the nobel prize years after her discovery.
What do mitogens do? give 3 exemple of mitogens
- it’s an extracellular signals that is necessary for cell proliferation.
- They increases cyclin synthesis, and thus Cdk activation.
- They promotes entry into S-phase from G1
- e.g. PDGF, EGF, erythropoietin (EPO).
What causes tumors to keep growing?
- Mutations can sometimes lead to abnormal mitogenic stimulation.
- Excessive increase of Ras or Myc mimics stimulation.
How does a cell go past the G1 restriction point in it’’s cycle?
requires an extracellular signal (mitogen).
Most vertebrate cells are in G0.
Describe the full mecanism by wich platelete derive growth factor mitogens stimulate cell division
- Mitogen binds to PDGF receptor (tyrosine kinase)
- PDGF autophosphorylate using ATP
- Phosphorylated sites recruit and activates RAS (G-protein switch)
- RAS activates MAP kinase (“mitogen-activated protein kinase”)
- MAP kinase activates GRP (gene regulatory protein) by an unknown mecanism…
- GRP translocate in the nucleus and bind with myc gene, modifying it’s expression
- myc protein is produced that is a gene regulatory protein
- myc promotes the expression of the genes producing cyclin and SCF
- Cyclin activates G1-CDK
- SFC degrades P27 (a CKI) which in turn activates S-CDK
- all those CDK phosphorilate Rb (a protein that inhibites the cell cycle) therefore inactivating it
- The cell progress into S-phase
What prevents Abnormal Mitogenic Stimulation?
p53 is normally degraded when the cell is normal but if there’s excessive Myc production, p19ARF will bind Mdm2 and stabilize (release) p53.
This causes Arrest or apoptosis.
In cancer, this mechanism may not work because of p19 and p53 mutation.
What is a survival factor. give an exemple wherethose are important.
- Extracellular signals required for cells to survive.
- Secreted by cells in surrounding tissue.
- Without it, cells undergo apoptosis
- Some growth factors are survival factors.
- e.g. nervous system development.
Give the mecanism of survival factors pathway
- Survival factor links to receptor
- This phosphorylate PKB (protein kinase B) therefore activating it
- This leads to 2 things:
- Activates Bcl-2
- Normally, BAD is link to Bcl-2 and Bcl-2 is inactive
- The activated Bcl-2 will inhibite apoptosis
- Phosphorylates GRP (gene regulatory protein) therefore deactivating it
- Normally GRP allows the expression of cell death promoting genes that activate Apoptosis
- Activates Bcl-2
