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21 fall: Biochem > Test 2: Lecture 41 > Flashcards

Test 2: Lecture 41 Flashcards

1
Q

negative regulators of cell cycle are ___ for cancer

A

most common mutations

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2
Q

The cell cycle is a regular pattern of ____

A

growth, DNA replication, and cell division.

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3
Q

Cell cycle is a highly ___ and ___ process

A

evolutionarily conserved and extremely well-controlled process

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4
Q

The main mechanisms of control of the cell cycle are ___ and ___

A

checkpoints and feedback

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5
Q

if control mechanisms of cell cycle fail it leads to ___

A

cancer

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6
Q

The cycle works the same way in all tissues, but the ___ and ___can vary according to context and organismal needs

A

duration and frequency

cells can live for days or years. most cells are not actively dividing

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7
Q

Most tissue, differentiated cells, are actively being ___; some slowly, some quickly

A

renewed/ replaced

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8
Q

___ cells produce differentiated cells according to the needs of the tissue

A

Progenitor

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9
Q

The bone marrow produces ___ new neutrophils per day!

A

100 billion

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10
Q

Cells cannot keep growing without dividing or their ___: ___ will get too high very quickly

A

volume to surface area

cell likes high SA and low volume

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11
Q

Three stages of interphase

A

Gap 1 (G1): cell growth and normal functions

DNA synthesis (S): copies DNA

Gap 2 (G2): additional growth (chromatids
become replicated chromosomes)

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12
Q

after cell completes interphase it goes through ___ and ___ only is ___

A

mitosis and cytokinesis

cell is large enough and the DNA is undamaged

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13
Q

division of the cell cytoplasm

A

cytokinesis

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14
Q

3 major checkpoints of cell cycle

A

G1/S
• can DNA synthesis begin?

G2/M
• has DNA synthesis been completed
correctly?

• commitment to mitosis

spindle checkpoint
• are all chromosomes attached to spindle?
• can sister chromatids separate correctly?

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15
Q

what is the 1st checkpoint of cell cycle

A

G1/S
• can DNA synthesis begin?

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16
Q

what is the 2nd checkpoint of cell cycle?

A

G2/M
• has DNA synthesis been completed
correctly?

• commitment to mitosis

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17
Q

what is the 3rd checkpoint of cell cycle?

A

spindle checkpoint
• are all chromosomes attached to spindle?
• can sister chromatids separate correctly?

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18
Q

Checkpoints are based on activation and
inactivation of ___

A

cyclin-dependent protein
Kinases (CDKs).

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19
Q

CDKs are ___ until they are bound with ___ which activated the CDK.

A

cyclin-dependent protein
Kinases (CDKs)

inactive

cyclin

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20
Q

CDKs are regulated on the protein level by ___ and ___

A

cyclin-dependent protein
Kinases (CDKs)

CDK activating kinases(CAKs)

CDK inhibiting kinases (CIKs)

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21
Q

A cyclin-activated CDK has one or multiple
protein ___ target substrates

A

phosphorylation

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22
Q 
Phosphorylation usually leads to destruction of
the substrate (CKD and its cyclin) by \_\_\_\_
A

E3 ubiquitin ligase-mediated
degradation

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23
Q

p16, p27 work by

A

preventing CDK and its cyclin from binding to each other

inhibits cell cycle

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24
Q

Cyclins are primarily regulated on the ___ level. They are targets of transcription factors that become ___ and ___ in sequential fashion across the cell cycle

A

transcriptional

activated and inactivated (waves) one cyclin will lead to the activation of the next cyclin

cyclin D→ E→ A→ B

25
Q

Rb-E2F

A

When Rb is unphosphorylated, E2F transcription factor and Rb are attached and is inactive

Phosphorylation of Rb by CDK4/6 leads release of Rb from E2F,

E2F then can attach to DND and leads to activation of transcription of proteins that carry out cell cycle progression – both structurally and regulatory (make other CDK, help with mitosis and proteins that help cell cycle)

26
Q

Simplified view of role of Rb and E2F in the beginning of the cell cycle

A
27
Q

type of pro-growth cytokine or growth factor

A

mitogen

28
Q

External pro-division signals start with a ___ binding a surface receptor

A

mitogen

any type of pro-growth cytokine or growth factor

29
Q

Mitogen binding activates the receptor to initiate a signal transduction cascade that leads to transcription of cell cycle regulators such as ___

A

cyclin D.

used in first steps of cell cycle

cyclin D is needed to bind to CDK 4 to phosphorylate Rb to make it let go of E2F which allows E2F to bind to DNA and make more proteins that lead to further steps of cell cycle

30
Q

G1 checkpoint is which CDK and what inhibits this step

A

cyclin D/CDK 6

cyclin D/ CDK 4

p15,p18,p16,p19

cyclin E/CDK 2

p21, p27, p57

31
Q

S phase is triggered by __ and inhibited by __

A

cyclin A/ CDK 2

p21/p27/p57

32
Q

G2 is activated by ___ and inhibited by ___

A

cyclin A/ CKD 1

p21, p27, p57

33
Q

M phase is activated by ___ and inhibited by ___

A

cyclin B/CDK1

p21,p27,p57

34
Q

Cell cycle regulation can be simplified into the coordinated actions of three types of proteins:
___

A

(1) cyclins,
(2) CDKs
(3) inhibitors of cyclin-CDK complexes

35
Q

____ once activated, a cell cycle regulator activates things that activate it further

A

positive feedback

36
Q

once activated, a cell cycle regulator activates things that de-activate it

A

negative feedback

37
Q

restriction point of the cell cycle

A

GI check point

all or nothing check point

before this checkpoint cell needs growth factors to move forward, after this checkpoint there is enough + and - feedback to push the cell through cell cycle

38
Q

The ___ point defines a critical time in late G1 after which a cell is committed to undergo DNA replication and is no longer sensitive to growth-factor signaling.

A

restriction (R)

39
Q

After the R point, cell cycle progression can only be ___ by conditions of cellular stress, such as DNA damage or mitotic-spindle defects.

A

halted

checkpoints have to fail to stop cell from dividing

40
Q

Before the restriction point, the cell has a choice between cell division (growth) by continuing the cell cycle, and rest by going into ____

A

G0 (quiescence; not dividing indefinitely)

41
Q

G0 phase

A

G0 (quiescence; not dividing indefinitely)

not dividing or growing cell

42
Q

what CDK and cyclin are needed at each arrow?

A
43
Q

___ is the best studied and likely the
most important negative regulator of the
cell cycle and cell survival.

A

p53

44
Q

___ is the most commonly mutated gene
across all human cancers

A

p53

45
Q

p53 is a transcription factor that is directly negatively regulated by ___ (sequesters p53 in the cytoplasm)

A

MDM2

46
Q

p53 activates ___ as a critical negative feedback loop to prevent too much p53 buildup

A

MDM2

47
Q

p53 concentrations ___ based on ___; never all on or all off.

A

fluctuate

p53 activated MDM2, MDM2 inactivates p53

  • *Tipping this balance can tip cells toward**
  • *cell division, survival, or apoptosis**
48
Q

Steps of mitosis

A

PMAT

prophase

metaphase

anaphase

telophase

cytokinesis

49
Q

DNA is replicated in ___ of interphase

A

S-phase

50
Q

Further cellular growth in preparation for cell division occurs in ___ after DNA has been replicated

A

G2 phase

51
Q

Prophase

A

1st step of mitosis

During prophase, chromosomes condense and spindle fibers form.

52
Q

Metaphase

A

2nd step of mitosis

During metaphase, chromosomes line up in the middle of the cell.

53
Q

anaphase

A

3rd step of mitosis

During anaphase, sister chromatids separate to opposite sides of the cell.

54
Q

telophase

A

4th step of mitosis

During telophase, the new nuclei form and chromosomes begin to uncoil.

55
Q

Cytokinesis

A

division of the cytoplasm into two individual cells

56
Q

6 hallmarks of cancer

A
57
Q

Sustaining proliferative signaling is caused by mutation in ___

A

RAS

G protein.

It is active when bound to GTP and sends pro-growth signals to the nucleus

in healthy cell: growth factors cause, GTP hydrolysis, and RAS is then inactive

cancer cells: GTP is unable to hydrolysis. RAS stays active and cell gets continuous signal to grow and divide

58
Q

Evading growth suppressors by ___ mutations

A

PTEN

phosphatase

in health cell: PTEN will dephosphorylates PIP3 into PIP2 and stop signals to cell to divide

PIP3 activates AKT, which is a strongly pro-growth kinase that blocks expression of p27, p21 and other tumor suppressor genes.

in cancel cells: PTEN is mutated and PIP3 remains turned on and cell gets continuous signal to grow and divide

21 fall: Biochem (44 decks)

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