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BIOC 212 > Cell cycle > Flashcards

Cell cycle Flashcards

1
Q

What phases are considered as part of interphase?

A

Everything except cell division (M phase)
G1, S, G2 phases
*Interphase is much longer in time than M phase

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2
Q

In what phase does DNA replication occur?

A

S phase of the interphase

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3
Q

What are the different steps of mitosis?

A
  1. Prophase
  2. prometaphase
  3. metaphase
  4. anaphase
  5. Telophase
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4
Q

What happens during mitosis at the transition from metaphase to anaphase?

A

Abrupt change in biochemical state
The cell can pause in metaphase before this transition point, but one the point has been passed, the cell carries on to th end of mitosis and though cytokinesis into interphase

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5
Q

What is the difference between mitosis and cytokinesis?

A

Mitosis: Nuclear division
Cytokinesis: Cytoplasmic division of the cell at the end of mitosis

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6
Q

What are popular models of study for unicellular and multicellular organisms?

A

Unicellular: Fission Yeast and Budding Yeast

Multicellular: C. elegans and drosophila

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7
Q

How are the cell cycles of budding yeast and fission yeast different?

A

Fission yeast: same G1, S, G2, M phases, but during M phase, the nuclear enveloppe does not break.

Budding yeast: normal G1, S phases, but not nomal G2 phase (gradual transition from S → M phase) → microtubule based spindle begins to form inside the nucleus early in the cycle, during S phase. Cell divides by budding

Condensed mitotic chromosomes are readily visible in fission yeats, but less in budding yeast

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8
Q

What are the effects of temperature on the cell cycle?

A

At permissive (low) temperature, the cell divide normally, found in all phases of the cycle
At high restrictive temperatures → mutant gene product functions abnormally → cell cycle is stopped at the specific step that mutation affects

cdc mutant still continue to grow → abnormally large
non-cdc mutant eventually runs out

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9
Q

What is the effect of the cdc15 mutant on budding yeast cells?

A

They are stuck in anaphase → can see the large buds staying and not dividing

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10
Q

What is the process of growth of a frog oocyte?

A
  1. Oocyte grow without dividing (no DNA replication) for many months in mother’s ovary → matures into an egg (ready for fertilization)
  2. Fertilization
  3. Egg cleaves very rapidly (initially 1 division cycle/30min) → multicellular tadpole in 1-2 days
    *No G1 and G2 phases which makes the process much faster
  4. Cells get progressively smaller with each division, embryo remains same size
  5. Growth starts when tadpole begins feeding
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11
Q

Does the cell cycle absolutely have to be in a cellular environment to occur adequatly?

A

No, a cell-free mitotic cycle can be observed.
1. Activated frog eggs broken open by gentle centrifugation → separates the cytoplasm from other cell components
2. Undiluted cytoplasm is collected + sperm nuclei added to it + ATP → tube
3. Sperm nuclei decodes and goes through repeated cycles of DNA replication and mitosis
Conclusion: cell-cycle control system is operating in a cell-free cytoplasmic extract

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12
Q

How do mammalian cells look like in culture?

A

Most of the cells are spindle shaped, flat and attached
Some are round → going through mitosis

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13
Q

How can radioactivity be used to identify cell in the S phase in a sample?

A
  1. Expose the tissue for a short period to 3H-thymidine
  2. Visualize by autoradiography
  3. Silver grains (black dots) over a nucleus = cell incorporated 3H-thymidine into its DNA → was in S phase during labeling period
    *Presence of an S-phase cell is evidence of cell proliferation occurring (can be in response to damage)
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14
Q

How can cell proliferation be identified using fluorescence?

A

Immunofluorescence micrograph of BrdU-labeled glial precursor cells in culture
- Cells that were exposed to BrdU for 4h which incroporates into the DNA, then where fixed,
- Take a slice and exposed to fluorescent anti-BrdU Ab (red)
- All cells are stained with blue fluorescent dye

All cells appear blue, if they were in S-phase during exposition to BrdU, the nucleus appears red also

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15
Q

How can we do analysis of DNA content with flow cytometry?

A

Analysed cells are stained with a dye that becomes fluorescent when it binds to DNA → amount of fluorescnce ~ amount of DNA in each cell.
Uses a laser to fluoresce every cell 1-by-1 and sort them depending on their fluorescence

3 categories:
- unreplicated complement of DNA (G1 phase) → x1 relative DNA amount
- G2 or M phase → x2 relative DNA amount
- S phase are in between the 2 peaks

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16
Q

Where would cells that are dead by apoptosis and cancer cells appear on a flow cytometry graph?

A

Dead cells would have no DNA content to bind to → would appear between 0-1 relative amount of DNA/cell

Cancer cells replicate very fast and can have more copies of chromosomes → could appear 3-4 relative amount of DNA/cell

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17
Q

What is the G2 checkpoint associated with?

A

Entry into the M phase → trigger of the mitosis machinery → assembly of the mitotic spindle

Cell checks if all the DNA has been replicated with no mutations

*When passing through a checkpoint, cell can’t come back

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18
Q

What is the G1 checkpoint associated with?

A

Cell checks if the envrionment is favorable of DNA replication → triggers DNA replication machinery

*When passing through a checkpoint, cell can’t come back

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19
Q

What would happen to a cell that has no checkpoints in its cycle?

A
  • It would accumulate mutations because would divide (M phase) before they are all repaired (G2)
  • It would divide too quickly → become a cancer cell
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20
Q

What is the metaphase checkpoint associated with?

A

Are all chromosomes attached to the spindle? → trigger anaphase and proceed to cytokinesis → complete cell division

*When passing through a checkpoint, cell can’t come back

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21
Q

Can a cell go through the cell cycle without its checkpoints?

A

Yes, checkpoints are breaks for the cell to not pass to the next phase, they are not required for entry in the next phase

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22
Q

What is the cdk? And its role in the cell cycle?

A

cdk = cyclin dependent kinase → needs to be phosphorylated by kinase for its activation, on threonine of the T loop

  • cdk associates successively with different cyclins to trigger different events of the cycle
  • cdk acivity usually terminated by cyclin degradation
  • On single cdk for every phase, but different specific S-cyclins, M-cyclins, etc. → form S-cdk complex

*Same cdk for all the cycle, but activated by different cyclins specific to the phase

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23
Q

How many different cdk are there in budding yeast vs in vertebrates?

A

Budding yeast: Only Cdk1, several cyclin to make Cdk specific for each checkpoint

Vertebrate:
Different Cdks, all very similar
Different cyclins → very specific

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24
Q

How does cycling binding to Cdk → Cdk activation?

A
  1. Inactive state → without cyclin bound → active site is blocked by T-loop (region of the protein)
  2. Partial activation → caused by binding of cyclin which causes the T-loop to move out of the active site
  3. Fully active → phosphorylation of Cdk2 by CAK (Cdlk-activating kinase) at a threonine residue in the T-loop → changes the shape of the T-loop → improve the ability of the enzyme to bind its protein substrate → further activates the enzyme
    *Active site fully exposed so can act and phosphorylate its substrates
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25
Q

What is the whole process of M-Cdk activation (with its positive feedback loop)?

A
  1. Cdk1 + M-cyclin = inactive M-Cdk → levels gradually rise
  2. Cdk inhibitory kinase (Wee1) x2 + Cdk-activating kinase CAK phosphorylate M-Cdk → inactive Cdk (because of its inhibitory phosphates)
  3. At end of G2: Cdc25 (phosphatase) takes inhibitory phosphates → active M-Cdk (a lot at the time since they had accumulated)
    *Cdc25 has to be phosphorylated to be active

Positive feedback:
- Active M-Cdk further phosphorylates Cdc25
- Active M-Cdk inhibits Wee1

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26
Q

What is the role of CKI p27?

A

Active cyclin-Cdk complex → inactive p27-cyclin-Cdk

p27 binds to both cyclin and Cdk in a complex, distorting the active Cdk
Also inserts into ATP-binding site, further inhibiting the enxyme activity

Acts in checkpoints to inhibit the active cyclin-Cdk complex
*control of progression from G1 → S phases

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27
Q

How does M-cyclin trigger the mitotic machinery?

A
  1. M-Cyclin is upregulated → accumulates
  2. Binds to, and activates CDK → M-Cdk (kinase)
  3. M-Cdk (active kinase) will phosphorylate proteins responsible for mitosis → activate them
    *M-cyclin confers specificity to the kinase (kinase is the same for all phases)
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28
Q

How does Cdk use ATP?

A

Cdk = Kinase which catalyses the tranfer of gamma P of ATP (→ADP) → phosphorylate substrates (Ser/Thr)

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29
Q

What is the role of SCF

A

SCF = Ub E3 ligase
*Controls proteolysis

(unphosphorylated CKI can NOT bind SCF → regulation)
1. Phosphrylation of CKI (p27) allows to be recognized by SCF
2. With E1 and E2, SCF poly-Ub CKI
3. Ubiquitinylated CKI then recognized and degraded by proteasome

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30
Q

What is the role of APC

A

*Control of proteolysis → specifically M-cyclin Ubiquitylation (activated in late mitsosis

  1. Inactive APC is activated by Cdc20
  2. M-Cdk (M-cyclin + Cdk) + active APC + E1 + E2 + Ub → poly-Ub chain
  3. Degredation of M-cyclin in proteasome
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31
Q

What did cell fusion experiments show about the cell cycle?

A
  1. Fuse S + G1 phases → S-phase for both nucleus
  2. Fuse S + G2 phases → G2 nucleus stays in G2, S-phase nucleus continues DNA replication (No going back)
  3. Fuse G1 + G2 phases → Nucleus stay in their respective phases showing that factors of S-phase that did drive G1 are gone
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32
Q

What is the process of initiation of DNA replication

A

ORC (origin recognition complex) stays associated with a replication origin throughout the whole cell cycle.

  1. Early G1 → Cdc6 associates with ORC
  2. Mcm ring complexes (with Cdc6) assemble on adjacent DNA (binds ot ORC) → formation of pre-replicative complex
  3. Start of S phase: S-Cdk triggers origin firing → assemble DNA pol + proteins + activating Mcm migration along DNA strands (helicase) + Cdc6 is phosphorylated
    *ORC is phosphorylated for activation
33
Q

How is re-replication blocked?

A

S-Cdk also blocks rereplication by causing dissociation of Cdc6 from origins → phosphorylation of Cdc6 → degradation

Export of all excess Mcm out of the nucleus

34
Q

What are the levels of Cdl-cyclins like at the metaphase-anaphase of M-phase?

A

When the cells separates into 2 cells → No more Cdk activity, all cyclins are degraded
Then, the 2 spearated cells enter G1 where the levels stay close to 0, the cell fills its functions, until the cell gets the signal to enter another cell cycle

35
Q

What are the 3 major cyclins of the cell cycle? How do their concentrations oscillate vs Cdk?

A

Cdk is always constant and at higher levels than cyclins

G1/S-cyclin → G1/S-cyclin starts rising in late G1

S-cyclin → S-Cdk complex forms at the start of S phase, triggers DNA replication + early mitotic events, stays active during G2 phase as well

M-cyclin → M-Cdk complex forms gradually during G2, but held in an inactivve state, activated at the end of G2 → triger entry into mitosis at G2/M transition

36
Q

What 2 experiments demonstrate the requirement for protein degradation to exit mitosis?

A

Metaphase arrest (1) and Anaphase arrest (2)

  1. APC inhibition → arrested at metaphase → impossible dissociation of sister chromatids
  2. Nondegradable M-cyclin → arrested mitosis after sister-chromatid separation, degradation of M-cyclin required for subsequent exit of mitosis
37
Q

What are the structures and functions of cohesins and condensins?

A
  1. Both have identical DNA and ATP-binding domains on one side + hinge region the other side linked by antiparallel coiled coil → dimerize to form a V and bind and hold pieces of DNA together

Cohesin → glues 2 adjacent sister chromatids together
Condensin → mediates intramolecular cross-linking to coil DNA in the process of chromosome condensation

38
Q

What are the effect of activation of APC on metaphase-anaphase?
(Give set up)

A
  1. G2 = cohesin complex = attached sister chromatids (early mitotic event)
  2. In metaphase, spindles attach to the cohesin complex

*Securin binds to separase to make it inactive
Active APC:
- Acts as E3 ligase for poly-Ub → degredation M-cyclin
- E3 ligase for securin → degradation → active separase → cleaves subunit of cohesin → sister chromatids can separated

39
Q

What is the role of Polo kinase

A

It phosphorylates the cohesin complex to facilitate cohesin cleavage → provides additional control on the timing of the metaphase-to-anaphase transition

40
Q

What is Mad2 protein ?

A

It binds to the kinetochore of chromosomes that are not attached to spindles at metaphase → signal to not go through metaphase-anaphase

41
Q

COME BACK TO SLIDE 31

A
42
Q

What is the effect of Hct1-APC activity in G1?

A

Maintains APC activity during anaphase + G1 → ensures supression of Cdk activity during G1 and anaphase (for M-Cyclin)

Faster exit of meiosis, no entry into the next cycle right away

43
Q

What are the effects of Sic1 and Hct1-APC in the control of G1 progression in budding yeasts? (Start and end of G1)

What is the the mechanism for their inactivation?

A

*Sic1 = equivalent of p27 in mammlian cells
phosphorylated Sic1 and Hct1 = inactive

Active Sic1 and Hect1-APC → M-Cdk inactivation (from end of M → G1, exit from mitosis) → stable Cdk inactivation during G1

When right conditions for entering a new cell cycle:
Active G1-Cdk → active G1/S-Cdk → inactivation (phosphorylation) of Sic1 and Hct1 → active S-Cdk
Phosphorylated Sic1 recognized by SCF (E3 Ub ligase)

44
Q

What is the initiator of the cell cycle?

A

G1-Cdk complex

45
Q

What mechanism is responsible for control of S-phase initiation in animal cells?

A
  1. G1-Cdk activity → Rb phosphorylation → inactivates Rb → free E2F → activates transcription of S-phase genes (including G1/S-cyclin and S-cyclin)

Positive feedback loops:
1. further enhances phosphorylation of Rb
2. E2F stimulates transcription of its own genes

*Active Rb wraps around E2F to inactivate it
*That pathway is always affected in cancers

46
Q

What happens to cells if the cell cycle has no nutritional control in yeasts?

A

The cells become smaller and smaller as they don’t wait to have enough nutrients to divide

With nutritional cell-cycle control → the cell waits longer to divide when reduced nutrition

47
Q

How does DNA damage arrest the cell cycle in G1?

A
  1. When DNA damaged → protein kinase activation → phosphorylation of p53 → Mdm2 (E3 ligase) can’t bind to p53, so accumulation of p53
  2. Active p53 binds to regulatory region of p21 gene
  3. p21 (Cdk inhibitor protein, CKI protein) is expressed → inactivates the G1/S-Cdk or S-Cdk complexes → blocks entry into S phase

DNA damage → phosphorylation of Mdm2 or decrease in Mdm2 production

In normal conditions:
Mdm2 binds to p53 → promotes Ub and destruction in proteasome → levels of p53 kept very low

48
Q

What are the different checkpoints of the cell cycle? What do they act on?

A

Start of G1:
- Unfavorable extracellular environment → G1-Cdk
- DNA damage → p53
- Excess mitogenic stimulation → p53
G2:
- Unreplicated DNA + DNA damage → Cdc25 → M-Cdk
End of M phase:
- Chromosome unattached to spindle → APC

49
Q

How can apoptosis be physiological?

A

Can be induced during tissue growth:
- Separation of fingers
- During metamorphosis of a tadpole into a frog → tail loss (induced by increase in tyroid hormone in the blood)

50
Q

What is the difference between necrosis and apoptosis?

A

Both cell death mechanisms:
Necrosis → not controlled, cell “explodes”, dangerous for neighbouring cells

Apoptosis → cell in relatively intact, intracellular contents are degraded and recycled → eaten by a phagocytic cell

51
Q

What is the role of mitogens?

A

Mitogens stimulate cell division (come mitogens are also growth factors, but not the same)

  1. Bind to the cell surface (mitogen receptors on the extracellular side) → activation of Ras → MAP kinase cascade → activation of gene regulatory protein (enters the nucleus)
  2. This pathway causes increased production of the gene regulatory protein Myc
  3. Myc increases transcription of several genes, including cyclin D (G1 cyclin) + SCF Ub ligase
  4. Increase in G1-Cdk and G1-S-Cdk → Rb phosphorylation + activation of E2F → S-phase entry
52
Q

What is the role of Myc

A

Promotes DNA replication → increases transcription of several genes:
1. Cyclin D → G1-Cdk (CyclinD-Cdk4) activation
2. SCF Ub ligase → increased p27 degradation → G1/S-Cdk activation
1 and 2 → Rb phosphorylation → increased E2F activity → entry into S phase
3. E2F gene → entry into S phase

*Myc function as a heterodimer with Max protein

53
Q

What is the effect of excessive stimulation of mitogenic pathways?

A
  1. Excessive Myc → activation of p19 ARF → binds to/inhibits Mdm2 → increased levels of p53 → cell cycle arrest or apoptosis depending on extracellular conditions
54
Q

By what pathway can extracellular growth factors promote cell growth?

A

GF binds to GF receptor → activation of PI 3-kinase → activation eIF4E + activation phosphorylated S6 kinase → increased mRNA translation → increase protein synthesis

*Growth factors can also inhibit protein breakdown by poorly understood pathways

55
Q

What is the importance of cell communication?

A

Necessary for growth, migration and differentiation of cells in the embryo and their tissue organisation

Orchestrate normal cellular behaviour and responses to infections

Defects un cell communication can cause cancer, diabetes, disorders or immune and cardiovascular system

56
Q

What are the 4 steps for cellular interactions?

A
  1. Production of a signalling molecule
  2. Activation of the receptor
  3. Biochemical changes resulting in signal transduction
  4. Signal sent to nucleus to affect gene expression (in many cases)
57
Q

What are the 5 classes of ligands? (growth factors/hormones)

A

*Classified according to the distance over which they act

  1. Autocrine → stimulates same cell
  2. Paracrine → stimulates cells in close proximity
  3. Endocrine → at a distance (hormones travelling through the blood)
  4. Synaptic → Specific to nerve cells
  5. Juxtacrine → direct contact, mostly in the brain (signalling molecule could be a TM protein on the surface of the cell)
58
Q

What is the importance of combinatorial signalling?

A

No signals at all → programmed cell death
Some specific combinations → survival
Some other combinations → proliferation

Cells are exposed to many ligands, only respond to some of them
Most cells depend on a specific set of ligands to avoid cell death

59
Q

Does 1 ligand always produce de same response on every cell it binds to?
Give an example

A

The ligand does not determine the response, the receptor does, concentration of the ligand also does.

Protein A → response A
Protein B → response B
Protein A + B → response C

Ex:
Ach binding to skeletal muscle cells → contraction
Ach binding to heart muscle cells → relaxation (different receptor)
Ach binding to secretory cell → secretion (same receptor)

60
Q

In what cases would ligand receptors be found in the cytoplasm or nucleus?
What are the receptors associated to them

A

Small hydrophobic/liposoluble ligands can diffuse through the cell membrane

Receptors = steroid nuclear receptor family → direclty regulate gene transcription

Ex of ligands: estuarial, testosterone, vitamine D3, retinoic acid

61
Q

What are the characteristics of the intracellular receptor superfamily ?

A

ALL have DNA binding domain (look similar, but binds to different sequences) + hormone binding domain (very different, specific for each hormone)

In inactive form → bound to inhibitory protein complex which blocks the DNA-binding side
When Steroid hormone binds → conformational change → removes inhibitory protein complex → DNA-binding site is exposed

62
Q

What are the characteristics of ligands that bind to the cell suface receptors?
Give examples

A
  • Hydrophilic (can’t pass the hydrophobic membrane)
  • frequently small molecules
  • peptides 6-20 kDa in size
  • Most growth factors are small proteins, some growth factors are large proteins (90 kDa Hepatocyte growth factor)

Ex: Neurotransmitters, Growth factors (small proteins),

63
Q

What are the 3 classes of cell surface receptors? (for hydrophilic ligands)

A

Ion-channel-linked receptor:
- Ligand open or close ion channel (mechanical)
- Involved in rapid synaptic signaling
- No enzymatic activity

G-protein-linked receptor:
- Use trimeric G protein as an intermediate to regulates activity or another membrane bound molecule (binding of the ligand activated the G protein which goes to its next target protein and activates it)
- Often associated with kinase acitivity inside the cell

Enzyme-linked receptor:
- Have enzymatic activity or are associated with enzymes when activated
- binding of the ligand activates catalytic domain on the intracellular side of the receptor

64
Q

What is the general structure of enzyme linked cell surface receptors?
What are the 4 classes of enzyme coupled receptors?

A

General structure → ligand recognition domains (extracellular) + kinase domains (intracellular)

4 classes of intracellular kinase domains:
1. Receptor tyrosine kinases
2. Receptor tyrosine kinase associated receptors
3. Receptor serine/threonine kinases
4. Receptor tyrosine phosphatases

*Multiple subfamilies of each receptor

65
Q

What are characterstics shared by many receptors for growth and differentiation factors?

A

Transmembrane receptor Tyrosine specific protein kinase

3 domains in receptor tyrosine kinase:
1. Extracellular domain (N-terminus) → large and glycosylated, binds to the growth factor
2. TM domain → short and composed of hydrophobic amino acids
3. Intracellular domain (C-terminus) → contains the catalytic kinase domain

66
Q

What is a difference between tyrosine-specific protein kinase and serine/threonine-specific protein kinases receptors?

A

tyrosine-specific protein kinase receptors → mostly transmembrane

serine/threonine-specific protein kinases receptors → mostly intracellular receptors

67
Q

How does binding of a protein to the extracellular portion of a Receptor Tyrosine Kinase, regulate the catalytic domain on the ther side of the protein?

A
  1. Growth factor binding → receptor tyrosine kinase dimerization
  2. Dimerization → transphosphorylation of receptors on the intracellular side (at specific tyrosines for specific proteins)
  3. Phosphotyrosines act as docking sites for SH2 containing proteins
  4. Some of those are themselves phosphorylated by the receptor
68
Q

What are the SH2 and SH3 domains and their functions?

A

SH2 (for Src Homology 2) and SH3 are small proteins/domains
- SH2 ~ 100 aa, SH3 ~ 50 aa
- SH2 binds phosphotyrosines of RTK kinase domain
- SH3 binds proline rich proteins (modifies the signal, recruit other proteins to refine the signal)
- Usually shared by the various intracellular substrates of RTK (receptor tyrosine kinase)

69
Q

What determines specificity of the substrate binding to the receptor tyrosine kinase?

A

The primary sequence of the kinase domain as only tyrosine residues are phosphorylated → phosphorylation sites of the receptor determin which substrate binds

70
Q

What is the role of the Ras protein in the intracellular signaling cascades activated by receptor tyrosine kinases?

A

*Ras often activated by RTK
Acts as a crucial link → relay signals from receptor tyrosine kinase → nucleus to help stimulate cell proliferation or differentiation

*Other type of signal coming out of this cascade, as phosphorylation acts more to activate transcription of specific genes
(GNRP = GEF)

71
Q

What are the steps of the relay of signals from the Activated receptor tyrosine kinase to the nucleus?

A
  1. Grb2 (has SH2 domain)/Sos bind to phosphorylated residues
  2. Sos mediated GDP/GTP exchange on membrane ras
  3. ras-GTP binds to Raf → MAP kinase cascade
  4. MAPK-p enters the nucleus → phosphorylates elk/tef → activated transcription
72
Q

What protein is responsible for de-phosphorylation of the intracellular part of RTK?

A

protein phosphatase

73
Q

What proteins are involved in regulation of S phase entry?

A
  1. Rb phosphorylation → E2F (activates)
  2. Phosphorylation of p53 (inhibits)
  3. ORC/Cdc6/Mcm complex (process of replication)
74
Q

Explain the hypothetical model of how budding yeast cells might coordinate cell growth and cell-cycle progression?

A
  1. The cell contains fixed # of proteins bound to DNA
  2. These proteins also bind G1-Cyclin (Cln3) and inhibits it
  3. As the cell grows, total Cln3 increases in parallel with total cell protein:
    - When cell is small, all Cln3 is inactivated and binds to excess Clin3-binding-protein (on DNA)
    - When cells is bigger Cln3-binding-proteins saturate → free Cln3 in the cell (G1-cyclin) → Cdk activation → S phase
75
Q

What are difference in protein levels between embryonic cells with no G1 phase vs cells with G1 phase?

A

G1 is created by stable Cdk inhibition after mitosis

Embryonic w/ no G1: Cdc20-APC activity rises at end of metaphase → M-cyclin destruction → loss of M-Cdk → APC inactivation after mitosis → allow M-cyclins to accumulate again

Cells with G1 (same start): Cdc20-APC activity rises at end of metaphase → M-cyclin destruction → activation of Hct1-APC (+ accumulation of other CKI) → supression of Cdk activity after mitosis

76
Q

What is required for entry into anaphase?

A

Degradation of M-cyclin by APC
If M-cyclin can’t be degraded, chromatid sisters can be spearated, but cell can’t exit mitosis

77
Q

What is the difference between p21 and p27?

A

Both are CKIs
p21 = transcriptionally activated by p53, for DNA damage in G1 → binds to inactivate G1/S-Cdk and S-Cdk
- Can promote apoptosis

p27 supresses G1/S-CDK and S/Cdk in G1
- Helps cell to withdraw from cell cycle when terminally differentiated

78
Q

How is p27 degraded?

A
  1. Phosphorylated by Cdk2
  2. Recognized by SCF → poly-Ub
  3. Degradation
79
Q

By what pathways can survival factors affect apoptosis?

A
  1. Survival factor binds to receptor → phosphorylates/actives PKB →
  • Phosphoorylates (for degradation) genes that promote cell death
  • Bad binds to Bcl-2 to inactivate it. Active PKB phosphorylates/inactivates Bad → can’t bind Bcl-2 → active Bcl-2 → inhibits apoptosis

BIOC 212 (15 decks)

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