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Isaak: Biochemistry MBS > Lecture 12: Biochemistry of Cancer > Flashcards

Lecture 12: Biochemistry of Cancer Flashcards

1
Q

What chromosome can one find the Rb gene?

A

Chromosome 13

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2
Q

An individual with a deletion of one Rb+ allele is said to be _____.

A

Predisposed to developing retinoblastoma.

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3
Q

Loss of both Rb+ alleles…

A

…induces tumor formation.

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4
Q

True or false?

Loss of the Rb gene is found only in retinoblastoma cases.

A

False.

The Rb gene is frequently missing in several other types of cancer as well.

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5
Q

What are the two forms of retinoblastoma?

A
  1. Hereditary.

2. Sporadic.

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6
Q

E2F

A

A transcription factor that helps transcribe genes whose products are required for the S-phase of the cell cycle.

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7
Q

pRB

A

The protein product of the Rb gene.

When UN-phosphorylated, it is bound to the transcription factor E2F.

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8
Q

Phosphorylated pRB

A

Dissociates from E2F, allowing it to exert its effects on the transcription of S-phase-dependent proteins.

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9
Q

Unphosphorylated pRB

A

Is bound to E2F, keeping it from exerting its effects on the transcription of S-phase-dependent proteins.

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10
Q

Cyclin D and Cyclin E

A

Bind with cyclin-dependent kinase (CDK) to phosphorylate pRB.

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11
Q

What happens in the absence of pRB?

A

E2F is left unbound, therefore exerting its effects on the up-regulation of S-phase dependent proteins.

Cells, even with damaged DNA, can continue to replicate.

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12
Q

Many anti-proliferative signals are funneled through which protein?

A

pRB.

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13
Q

Which protein is the substrate for many “stress-related” phosphorylation events?

A

p53.

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14
Q

RE

A

Response element. Usually in reference to the regulatory region where p53 binds.

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15
Q

Once DNA damage is detected (or an oncogene is expressed), what protein is activated?

A

p53.

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16
Q

What are the two outcomes after p53 has been activated?

A
  1. Apoptosis

2. Activation of p21

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17
Q

p21 (two functions)

A

Activated by p53 when DNA damage is detected.

  1. Inhibits cyclin/CDK complexes, which in turn halt the cell cycle.
  2. Binds to PCNA (clamp), inhibiting progression of replication forks.
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18
Q

Many cancer cells do not undergo apoptosis due to what is thought to be an absence of what protein?

A

p53.

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19
Q

What type of cancer(s) does the following tumor suppressor, when dysfunctional, cause?

RB

A

Retinoblastoma

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20
Q

What type of cancer(s) does the following tumor suppressor, when dysfunctional, cause?

p53

A
  1. Sarcomas

2. Carcinomas

21
Q

What type of cancer(s) does the following tumor suppressor, when dysfunctional, cause?

NF1

A

Neuroblastoma

22
Q

What type of cancer(s) does the following tumor suppressor, when dysfunctional, cause?

APC

A
  1. Colon

2. Stomach

23
Q

What type of cancer(s) does the following tumor suppressor, when dysfunctional, cause?

BRCA 1

A

Breast Cancer

24
Q

In regards to an oncogene, how many of the cell’s copies need to be altered?

A

Only one. This is a “dominant effect.”

25
Q

Signal Transduction

A

The movement of signals from outside the cell to the nucleus.

26
Q

What does signal transduction have to do with cancer?

A

Tumor cells generate many of their own growth signals.

27
Q

What is sis and where was it originally discovered?

A

Simian sarcoma oncogene; discovered in a transforming retrovirus.

28
Q

What does sis encode?

A

Part of the PDGF (a tyrosine kinase), which is able to induce signal transduction.

29
Q

What is EGF and it’s role in cancer?

A

Epidermal growth factor. Mutant forms of the EGF receptor are known to constantly stimulate growth, even in the absence of EGF.

30
Q

What are family members of EGF?

A

Erb/HER2.

31
Q

What is Ras?

A

A signaling molecule that is important in signal transduction to the nucleus.

32
Q

When GTP is bound to Ras, it is said to be ____.

A

Active.

33
Q

When GDP is bound to Ras, it is said to be ____.

A

Inactive.

34
Q

What is GAP?

A

GTPase Activating Protein

35
Q

What does the NF1 gene encode?

A

NF1 encodes a protein called neurofibromin, which contains a GAP domain.

36
Q

Describe what happens in NF1.

A

Neurofibromin is altered, which results in a defective GAP domain that is supposed to deactivate Ras and its signaling pathway to the nucleus.

37
Q

What three important transcription factors interact with the signal transduction pathway?

A

FOS, JUN, and MYC.

38
Q

How are FOS and JUN related?

A

They need to bind to one another to form AP1, which can then bind to DNA.

39
Q

AP1

A

A heterodimer of FOS and JUN.

40
Q

How are FOS and JUN related to cancer?

A

Over-expression of these two factors can result in elevated transcription of growth-dependent genes, and ultimately, continuous (instead of transient) cell growth.

41
Q

Neurofibromatosis

A

Neuofibromas appear on the skin, also called cafe au lait spots.

42
Q

What is Myc?

A

Myc is a gene that encodes a transcription factor that regulates the expression of 15% of all genes.

43
Q

What are two roles of MYC?

A

MYC binds to enhancer sequences (e-boxes) and recruits histone acetyltransferases (HATs).

44
Q

What occurs as a result of certain mutated forms of Myc?

A

Up-regulation of genes, some of which are involved in cell proliferation.

45
Q

What is the cytogenetic etiology of Burkitt’s lymphoma?

A

A translocation between chromosome 8 and one of three chromosome (2, 14, and 22) that encode antibody molecules.

When translocated, the Myc gene is constitutively (constantly, regardless of need/demand) expressed.

46
Q

How does a DNA tumor virus work?

A

It sequesters Rb and p53, causing cell proliferation by freeing cell proliferation transcription factors.

47
Q

What are the six hallmarks of cancer?

A
  1. Evading apoptosis.
  2. Self-sufficiency in growth signals.
  3. Insensitivity to anti-growth signals.
  4. Sustained angiogenesis.
  5. Limitless replicative potential.
  6. Tissue invasion and metastasis.
48
Q

Familial APC

A

Familial adenomatous polyposis coli

Isaak: Biochemistry MBS (11 decks)

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