Lecture Set 20 Flashcards
Describe the 5 phases of the cell cycle and the cell checkpoint
G0 –> resting phase
G1 –> protein/RNA synthesis (Gap phase)
Restriction checkpoint (late G1) –> committal to synthesis, influenced by cell size, growth factors, committal to entering cell cycle
S –> DNA synthesis
G2 –> protein/RNA synthesis
G2 checkpoint –> influenced by cell size, DNA replication complete
M –> mitosis
Metaphase-to-anaphase checkpoint –> are microtubules connected to kinetochores
Describe the stages of mitosis
Prophase –> chromosome condensation, separation of centrosomes, nucleation and elongation of spindles
prometaphase –> degradation of nuclear membrane. phosphorylation of nucleoporins to enhance dissociation of nuclear pore complexes, phosphorylate inner nuclear membrane proteins to inhibit interaction with chromatin and lamin, phosphorylate chromatin and lamin to induce depolymerization, chromatin condensation
Spindles push and pull on chromosomes during chromosome congression
metaphase–> chromosomes lined up at metaphase plate
anaphase –> separation of sister chromatids
done through two ways –> depolymerization of kinetochore microtubules (chromosome-to-pole movement) combined with motor proteins at the kinetochore; pole separation due to elongation of interpolar microtubules producing a sliding force between microtubules and a pulling force at the poles
telophase/cytokinesis –> dephosphorylation, reproduction of nuclear membrane, cleavage furrow formed of contractile ring of actin/myosin, chromosomes decondense and spindles disassemble
What is TOR?
target of rapamycin, a kinase that stimulates molecules involved in cell growth and cell cycle progression
How is progression through the cell cycle controlled?
Cdks (cyclin-dependent kinase) and cyclin
kinases are always present in constant levels, cyclin levels fluctuate
The cyclin-Cdk complexes trigger cell cycle events
Describe how a M-Cdk is formed, as well as how it is regulated
Cdk and cyclin bind, then a CAK (CDK activating kinase) and a CDK inhibitory kinase, such as Wee-1, add inactivating and activating phosphates. Then, cdc-25 phosphatase removes the inactivating phosphates to activate the cyclin-CDK after it itself is phosphorylated.
M-Cdk then goes on to phosphorylate the nuclear Lamins to disrupt integrity of the nuclear envelope
Besides phosphorylation, how can Cdk be regulated?
Cdk inhibitory proteins such as p27 bind to the cyclin-CDK complex to distort the active site
How is metaphase-to-anaphase checkpoint passed?
cyclin degradation by the APC
APC = anaphase promoting complex, must be activated by cdc20
ubiquitylation by ubiquitin ligase of S and M cyclin tags it for destruction by APC
APC also ubiquitylates and destroys securin. securin inhibits separase, which destroys the cohesins binding the two sister chromatids together, allowing for separation
How is cell division and growth regulated by mitogens?
G1-Cdk activity is blocked, mitogen binds to receptors to release the block via cascade, allows Cdk to phosphorylate of Rb (Retinoblastoma) protein and activation of E2F proteins. E2F binds to promoters to allow for transcription of S-proteins.
P16 binds to G1-Cdk to inhibit it.
Lack of p16, overproduction of G1-Cdk, or lack of Rb can be oncogenic
Describe the two pathways of apoptosis
1) extrinsic. Fas ligand on lymphocyte binds to Fas receptor, creates scaffolding to cluster proteins together to activate procaspase 8 or 10, leads to caspase cascade eventually to executioner caspase
2) intrinsic. through internal signals, either lack of survival factors, or through DNA damage leading to phosphorylation of p53 binding to DNA and stimulates transcription of p21 (a CKI) leading to release of cytochrome c from the mitochondria leading to activation of procaspase 9 and a caspase cascade leading to executioner caspase.
What are some of the benefits of apoptosis?
1) eliminate unwanted cells during development –> removes webbing between fingers
2) quality control –> eliminates improper cells
3) ex. nerve cells, way too many cells at start, but through lack of survival factors, extraneous cells are killed off but ensures that all target cells are innervated
