Lecture 12 Cell cycle and death Flashcards
the cell cycle
- cell growth and chromosome replication
- chromosome segregation
- cell division
interphase
M phase
interphase: G1, S, M
M phase: mitosis + cytokinesis
mitosis
prophase metaphase anaphase telophase
control systems of the cell cycle
3 major regulatory checkpoints:
Start = restriction point: in the late G1, cell commits to chromosome duplication
G 2/M point: system triggers chromosome alignment
metaphase-to-anaphase transition: system stimulates chromatide separation and pushes to the completion of the cycle and initiation of cytokinesis
the cyclins
- G1/S cyclins trigger progression through start point
- S cyclins trigger DNA replication
- M-cyclins trigger mitosis
- APC/C complex triggers anaphase
each cyclin activates specific cyclin-dependent protein …
kinases
The level of Cdks is constant (constitutive) in the cell, but the level of … change.
cyclins
The oscillation in levels of cyclins (synthesis and degradation) is the main mechanism for regulating the Cdks activity, but not the only one. Other important mechanisms are also involved:
- phosphorylation of the cyclin-Cdk complex by the kinase Wee1 inhibits its kinase activity
- dephosphorylation of the same residues by the phosphatase Cdc25 increases the activity
- binding of Cdk inhibitor proteins (e.g. p27) to the complex rearranges the active site of the kinase and renders it inactive
Onset of mitosis depends mainly on the protein kinase M-Cdk. When activated, M-Cdk activates the following processes:
- induction of assembly of mitotic spindle
- attachment of sister chromatides to the opposite poles of the spindle
- chromosome condensation
- breakdown of nuclear envelope
- rearrangement of actin cytoskeleton and Golgi apparatus
activation of M-Cdk
M-cyclin gradually accumulated in the cell
Cdk1 in complex with M-cyclin gets phosphorylated by CAK, catalyzed by Wee1
inactive complex building up
Phosphatase Cdc25 removes the inhibitory phosphate
-> M-Cdk complex active
+ two positive feedback loops
M -Cdk initiates the spindle assembly in …
Prophase
Spindle attaches to … on chromosomes
kinetochore
prophase
1
prometaphase
2
metaphase
3
anaphase
4
telophase
5
cytokinesis
6
Apoptosis
programmed cell death
Elimination of damaged or infected or cancer cells Correct creation of organs and limbs
Caspases
Regulation of initiation of apoptosis
initiator caspases
executioner caspases
Activation of caspase cascade:
extrinsic pathway (from outside) intrinsic pathway (from inside)
proapototic
anti-apoptotic
proapototic - increase cyt c release
anti-apoptotic - inhibit the release of cyt c
what causes tumors?
increased cell division or decreased apoptosis
