Exam 4: Cell Cycle Flashcards

1
Q

M phase

A

Mitosis - cell divides into two daughter cells

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2
Q

Interphase

A

time between mitosis

G1, S, and G2 phases

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3
Q

G1 phase

A

growth period precedes DNA synthesis

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4
Q

S phase

A

DNA is replicated only one time

At end, each chromosome has two identical sister chromatids linked by centromere

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5
Q

G2 phase

A

Second period of growth that precedes cell division

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6
Q

G0

A

cells are differentiated and no longer dividing

exited cell cycle, some cells can re-enter cell cycle when stimulated

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7
Q

G1/S checkpoint

A

start or restriction point

cell determines if conditions are favorable for division

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8
Q

G2/M checkpoint

A

ensures that all DNA has been replicated

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9
Q

Metaphase/anaphase transition point

A

All chromosomes are evaluated to ensure they are attached to mitotic spindle

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10
Q

DNA damage checkpoint

A

throughout cell cycle, detects damage to DNA

Cells with damaged DNA arrest until repairs are made, if damage can’t be repaired, cell enters apoptotic pathway

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11
Q

cyclin-dependent kinases (CDKs)

A

enzymes that function in association with regulatory subunits - cyclins
Active at different stages of cell cycle and regulate progression through phosphorylation of different protein targets

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12
Q

M phase uses what cyclin/CDK complex

A

Cyclin A/CDK1 and Cyclin B/CDK1

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13
Q

Mid G1 phase uses what cyclin/CDK complex

A

Cyclin D/CDK4 & 6

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14
Q

Late G1 phase uses what cyclin/CDK complex

A

Cyclin E/CDK2

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15
Q

S phase uses what cyclin/CDK complex

A

Cyclin A/CDK2

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16
Q

mitogenic signals

A

tissue-specific growth factors required to stimulate cell growth and division
Must overcome controls (like restriction point) in order to promote proliferation in most cells

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17
Q

Interactions between cell and extracellular matrix

A

promote cell division

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18
Q

Interactions between neighboring cells

A

inhibit cell division - contact inhibition

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19
Q

early response genes

A

genes transcribed in initial phase of cell, after adding growth factor

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20
Q

c-Fos transcription factor

A

early-response gene
stimulates transcription of the delayed-response genes (other transcription factors, mid-G1 cyclins & CDKs, late G1 cyclins)
transcription of c-Fos stimulated by MAP kinase cascade

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21
Q

growth factor binds to receptors containing

A

tyrosine kinase activity - triggers autophosphorylation of tyrosine residues, forms a docking site for other signaling molecules

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22
Q

GRB2

A

binds to phosphotyrosine residues on activated growth factor receptor
binds protein Sos, bringing it to cell membrane

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23
Q

Sos

A

brought to cell membrane by binding with GRB2 on growth factor receptor
interacts with Ras - promotes exchange of GDP to GTP activating Ras

24
Q

Ras

A

small G-protein
inactive in GDP-bound form, active in GTP-bound form
Activated by Sos
Activates protein kinase Raf

25
Q

Raf

A

protein kinase activated by active Ras

phosphorylates/activates MAP kinase kinase

26
Q

MAP kinase kinase

A

activated by active Raf

phosphorylates/activates MAP kinase

27
Q

MAP kinase

A

activated by MAP kinase kinase
enters nucleus and regulates transcription of many genes
stimulates c-Fos transcription, which leads to progression through restriction point

28
Q

Rb (retinoblastoma protein)

A

binds to protein products of delayed-response genes, E2F proteins, act as transcriptional repressors & inhibit transcription

29
Q

E2F proteins

A

protein products of delayed-response genes
transcription factors - activating transcription of many genes required for DNA replication
stimulate transcription of late G1 cyclin (cyclin E), S phase cyclin (cyclin A), S phase CDK (CDK2)
Inactive when bound to Rb

30
Q

Cyclin D-CDK4/6

A

Mid G1 phase cyclin/CDK complex
Promotes cell cycle growth by phosphorylating Rb, causing dissociation from E2F & activating E2F for transcription of genes & readying cell for S phase
Late G1 phase cyclin/CDK complex (cyclin E-CDK2) produced

31
Q

Cyclin E-CDK2

A

Late G1 phase cyclin/CDK complex
continues phosphorylation of Rb, promoting entry of cell into S phase
phosphorylates p27 triggers proteolysis of inhibitor & activation of Cyclin A-CDK2 complex

32
Q

INK4 proteins

A

compete with cyclin D for binding to CDK 4/6, act as specific inhibitor of CDK 4/6 activity

33
Q

p27 (KIP1)

A

inhibits cyclin A-CDK2 complex (keeps it in inhibitory state)
forms complex with cyclin A-CDK2 - frees complex when phosphorylated

34
Q

Cyclin A-CDK2

A

S phase cyclin/CDK complex
inhibited by forming complex with p27 (phosphorylated by cyclin E-CDK2)
Also requires dephosphorylation of internal inhibitor to be activated
When activated, DNA replication can begin - phosphorylates components of origins of replication to promote initiation of DNA replication

35
Q

Cyclin A/B-CDK1

A

M phase cyclin/CDK complex
held in inactive phase due to inhibitory phosphorylation of CDK 1 subunit until DNA replication is complete
Dephosphorylation activates complex - phosphorylates many substrates responsible for driving early part of mitosis (chromosome condensation, formation of mitotic spindle, and disassembly of nuclear membrane)

36
Q

Anaphase promoting complex

A

activated by attachment of chomosomes to mitotic spindle
leads to degradation of cohesion complexes that hold sister chromatids together at centromere
polyubiquinates cyclin A & B after anaphase is complete

37
Q

ATM

A

G2/M checkpoint
protein kinase detects replication forks - recognizes that DNA synthesis is still in progress
prevents dephosphorylation/activation of cyclin/CDK1 complexes
Also works with ATR as a DNA damage checkpoint; responds to double-stranded DNA breaks

38
Q

inhibition of anaphase promoting complex

A

by protein factors that recognize kinetochores not associated with spindle

39
Q

ATM/ATR

A

DNA damage checkpoints
inhibits phosphatases that normally dephosphorylate and activate cyclin/CDK2 and cyclin/CDK1 complexes - block progression of cell cycle
Phosphorylates/stabilizes p53

40
Q

ATR

A

DNA damage checkpoint

activated by DNA damage caused by UV light and certain drugs

41
Q

p53

A

transcription factor stabilized from phosphorylation by activation of ATM/ATR
Activates p21, which inhibits both cyclin/CDK1 and CDK2 complexes - prevents cell growth
Intrinsic activator of apoptosis

42
Q

p21

A

inhibitor of cyclin-dependent kinases

inhibits both cyclin/CDK1 and cyclin/CDK2 complexes - blocks S phase and mitosis

43
Q

Ataxia-telangiectasia

A

inherited disorder, difficulty in coordination of movement, small wide blood vessels, more susceptible to infection & chronic lung infections, leukemias, & lymphomas, highly sensitive to radiation exposure
Caused by mutation in gene encoding ATM - cell response to double strand DNA breaks is impaired

44
Q

Apoptosis

A

programmed cell death
removes damaged or infected cells from body
normal cell turnover, embryonic development & functioning of immune system
key means by which cytotoxic chemicals in cancer therapy work
Chromosome condenses, cell shrinks in size, nuclear envelope breaks up, cell fragmentation and blebbing occur (forming apoptotic bodies, which are then phagocytosed)

45
Q

tumor necrosis factor (TNF)

A

produced by macrophages & play role in cell death and tissue destruction - seen in chronic inflammatory diseases

46
Q

Fas ligand

A

produced by natural killer cells and cytotoxic T-lymphocytes

47
Q

caspases

A

family of proteases that are present as inactive precursors until apoptotic signal recieved
Initiator caspases activated by apoptotic signal and activate executioner caspases - hydrolyze cellular proteins & trigger DNA fragmentation

48
Q

Bcl-2 family

A

family of proteins involved in apoptosis - proapoptotic proteins
PUMA, BID, BAX

49
Q

Bcl-2

A

antiapoptotic protein
outer mitochondrial membrane protein
inhibits BAX

50
Q

BAX

A

protein that can form a channel in mitochondrial outer membrane
when stimulated allows release of cytochrome c from mitochondria into cytoplasm

51
Q

PUMA & BID

A

function to stimulate BAX activity

52
Q

Apaf-1

A

when bound to cytochrome c (released from mitochondria by BAX) it oligomerizates - results in formation of apoptosome

53
Q

apoptosome

A

formed by activation of Apaf-1 by cytochrome c

recruits and activates initiator caspase, caspace-9

54
Q

Caspase-9

A

initiator caspase
activated by apoptosome
activates caspase-3, executioner caspase

55
Q

Caspase-3

A

executioner caspase
activated by caspase-9
sets cell down path of programmed cell death