cell cycle, apoptosis and cancer Flashcards

1
Q

S phase of cell cycle

A

synthesis, chromosome duplication

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2
Q

M phase of cell cycle

A

Mitosis
- Chromosome
Duplication/Segregation
- Cytokinesis- Cell Division

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3
Q

Go Phase

A

Poor nutrient/environmental condition
cells withdraw from the cell cycle
Also occurs following terminal differentiation in certain tissue types (e.g. brain
neurons, cardiac muscle, RBCs)

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4
Q

interphase

A

(G1) = Gap 1 phase- RNA and protein synthesis needed for DNA replication
(S) Phase DNA synthesis
(G2) Gap 2 phase- DNA stability is checked

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5
Q

Restriction point cell cycle

A

between G1 and S phase

-if growth factors are limited

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6
Q

what are checkpoints in cell cycle?

A

1) restriction point
2) G1 checkpoint
3) metaphase checkpoint
4) G2 checkpoint

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7
Q

G1 checkpoint

A
  • Timing is similar to restriction point

- Occurs in response to DNA damage

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8
Q

G2 checkpoint

A

-Verify complete genomic duplication

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9
Q

metaphase checkpoint

A

-Ensures chromosomes attached to mitotic spindle

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10
Q

how does RB act as a tumor suppressor?

A

sequester E2F

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11
Q

What does entry from S phase to G1 require?

A

E2F to be active

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12
Q

what phosphorylates RB to make it inactive and activated E2F?

A

CDK2

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13
Q

what do cyclins require to be active?

A
  • cyclins

- CAK (t loop in cave site)

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14
Q

what expression rises and falls throughout the cell cycle?

A

Cyclin expression

-causes kinase activity to rise and fall

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15
Q

CDK4 and CDK6

A

helps the passage of cells through the restriction point in late G1 phase

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16
Q

Wee1 Kinase

A

inhibits Cdk activity by phosphorylating the roof site

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17
Q

Cdc25

A

dephosphorylates roof site to increase CDK activity

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18
Q

CKI (p27)

A

bind to Cdk and cyclin

-inhibits (G1 to S transition)

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19
Q

Metaphase to anaphase requires which key regulator?

A

APC/C (cyclosome)

-member of ubiquitin ligase family of enzymes

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20
Q

what does APC/C do?

A

-activated by Cdc20
addition of polyubiqutin to S and M cyclin complexes
-cyclins targeted for destruction by proteasome
-inactivates CdKs

21
Q

p53

A
  • activated by phosphorylation
    -leads to increased transcription of CKI (P21)
    p21= cell cycle arrest
22
Q

what keeps p53 inactive?

A

E3 ubiquitin ligase (MDM2)

23
Q

p21

A
  • is a CKI
  • primarily associated with inhibiting CDK2
  • major target of P53
24
Q

extrinsic (death receptor) pathway

A
  • Fas ligand activates FADD
  • Procaspase 8 to caspase 8
  • activates caspase 3,6,7
  • apoptosis
25
Q

intrinsic (mitochondrial pathway)

A
  • Caspase 8 active
  • release of cyt C from Mito
  • APAF-1 forms apoptosome
  • activates Caspase 9
  • activates caspase 3,6,7
  • apoptosis
26
Q

what are the initiators caspases

A

Caspase-8 and Caspase-9

27
Q

what are the executioner caspases

A

caspase 3

28
Q

what stimulates the intrinsic apoptotic pathway?

A
  • p53
  • BAX
  • BAK
29
Q

what inhibits the intrinsic apoptotic pathway

A

BCL2

BCL XL

30
Q

how does proto oncogene become an oncogene

A

gain of function mutation

31
Q

Her2 Receptor to oncogene

A

becomes oncogene after Val replaced with Gln

  • RTK activity always active
  • becomes NEU
  • breast cancer
  • Gain of Function
32
Q

EGF receptor to oncogene

A

deletion changes to EGFRvIII
RTK activity always active
-Glioblastoma

33
Q

ABL and BCR gene to oncogene

A

translocation creates BCR-ABL gene

  • acts as TF
  • Chronic myelogenous leukemia (CML)
34
Q

hereditary form of retinoblastoma

A
  • mutation/deletion in one copy of RB1 (heterozygous)
  • second hit required for cancer
  • loss of heterozygosity
35
Q

sporadic form of retinoblastoma

A
  • non hereditary
  • cancerous cell have both copies of RB1 mutated
  • rare
  • requires 2 indp. mutations
36
Q

loss of function mutations in tumor suppressor genes

A
  • p53
  • RB
  • APC
  • DCC
  • BRCA1/BRCA2
  • NF-1
37
Q

Metastasis Suppressors

A

Cell adhesion proteins

  • Prevent tumor cells from dispersing
  • Block loss of contact inhibition
  • Inhibit tumor metastasis
38
Q

Hallmarks of cancer cells

A

1) self sufficiency in growth signals
2) evading growth suppressors
3) activating invasion and metastasis
4) enabling replicative immortality
5) inducible angiogenesis
6) resisting cell death

39
Q

ex of a viral oncogene

A

HPV

40
Q

Viral oncogenes

A

proto oncogene infected by virus- viral genome integrates

  • virus replicates
  • protooncogene mutated to oncogene
  • can infect other cells
41
Q

alkylating agents

A
  • block DNA replication

- all phases of cell cycle

42
Q

antimetabolites

A
  • inhibit enzymes involved in DNA synthesis

- S phase

43
Q

Topoisomerase II inhibitors

A
  • S phase G2 phase M phase
44
Q

mitotic inhibitors

A
  • arrest cells in mitosis during metaphase

- M phase

45
Q

cytotoxic antibiotics

A
  • intercalate between bases in DNA to inhibit DNA synthesis

- S and G2 phase

46
Q

topoisomerase I inhibitor

A
  • S phase
47
Q

Herceptin

A

-targets HER2 receptor or NEU

48
Q

Gleevec

A
  • works with BCR/ABL enzyme and prevents phosphorylation of target protein
  • used in CML