EXAM 2 - Session 17: Cell Replication - Controlling Cell Number Flashcards
What are the steps of the cell cycle?
M - mitosis
Interphase - G1 to G2
* G1: Gap 1
* (G0: quiescent, non-dividing cells)
* S: Synthesis of DNA
* G2: Gap 2
What occurs during G1 phase?
Cell growth
What happens during G0?
G0 occurs as part of G1 phase.
* long-term temporary or permanent halt of cell division
* post-mitotic –> still biochemically active
* some cells have VERY long G0 –> not sure if they will even reach synthesis phase
What occurs during S phase?
DNA synthesis
* DNA poly. and genome replication
What occurs during Gap 2 phase?
Preparation for cell division
* chromosomes align and preplare for mitosis
What are the sub-steps of M-phase?
Prophase - chromosomes condense
Prometaphase - nuclear membrane breaksdown
Metaphase - chromosomes align at metaphase plate
Anaphase - chromosomes seperate to opposite poles
Telophase - nuclear membrane reforms around each daughter cell.
Explain what it means when a cell is post-mitotic.
- “terminally differentiated”
- Can’t divide anymore
- ex: upper layers of epidermis, many neuronal cells, skeletal muscle, RBCs
Define a quiescent cell.
- indefinitely stopped
- some can be triggered to divide with the right signal
- can reenter the cell (mitotically active)
What is the External Positive Signal example focused on?
EGF - epidermal growth factor
* external signal –> internal signal –> consequence
* EGF protein **promotes skin cell replication **
* many NON-skin tissues produce and respond to EGF
Explain the mechanism of EGF signal transmission across membrane.
EGF receptor is a transmembrane glycoprotein with 3-sub units.
* Subunit 1 - extracellular receptor that projects from cell surface & binds EGF
* Subunit 2 - spans across lipid bilayer
* Subunit 3 - projects into cytoplasm & has kinase activity
What is the function of the intracellular sub-region of EGF receptors?
Attaches -PO4 gorups to tyrosine in itself & other proteins
Describe the signal cascade of External Positive Signals.
- ligand binding and dimer formation
- activation of receptor kinase and self-phosphorylation
- cytoplasmic proteins assoc w/ receptor are phosphorylated
- intracellular kinases activated & phosphorylate other cytoplasmic proteins (cascade)
- signal reaches inside the nucleus and causes transcription of genes encoding cell cycle promoting proteins: cyclins and Cdk’s
What is the significance of increased cyclin/Cdk activity?
Increased EGF = increased levels of Cdk = activation of multiple proteins
Describe the internal positive signals that occur after EGF-R.
Phosphorylation during signal cascade post EGF-R –> transcription of cell cycle-promoting genes
Explain cyclins.
Cyclins are regulatory subunit amounts that control the progression of a cell through the cell cycle by activating CDK.
Explain CDKs.
CDKs = cyclin dependent kinases
* catalytic subunit phosphorylates proteins
* activated when paired with cyclin
* possible cancer drug target
What happens when there is a lack of myostatin?
increased muscle mass!
* without myostatin, there is nothing that counteracts EGF cell replication
Explain the mechanism of myostatin.
- Myostatin binds to receptor.
- Receptor dimerization.
- recruitment of transmembrane ALK (kinase)
- ALK phosphorylates Smad
- phospho-Smad enters the nucleus
- binds promoter and increased transcription of cell cycle inhibitors p21 & p53
What are the specific internal negative signal effects of p27 and p21?
p27 and p21 both bind to and inactivate cyclins.
* blocks entry of new cyclin into S phase
* frequently mutated in cancers –> no brake (p21/27) = excess cycling
What must be true at G1 checkpoint?
- growth factors (external positive signals) present
- adequate cell size (sufficient components to distribute to daughter cells)
- nutrients available
If all these points are met, cell will continue to s-phase.
What must be true a G2 checkpoint?
- adequate cell size
- chromosome replication is complete (ensure no loss of genes to daughter cells - are daughter cells complete?)
If yes to these points, cell can move on to metaphase checkpoint
What must be true at metaphase checkpoint?
- all chromosomes are attached to functional mitotic spindle (if we have a metaphase plate established and chromosomes are attached to the spindle, will they successfully divide? –> divide into two daughter cells)
If yes, the cell will then divide into two complete daughter cells
