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Physiology > Oncogenes and apoptosis > Flashcards

Oncogenes and apoptosis Flashcards

1
Q

what is apoptosis?

A

Physiologica cell death

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2
Q

Name 4 situations when the apoptosis of cells occurs

A

Redundant cells
Damaged cells
Obsolete cells
Harmful cells

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3
Q

In what physiologic state is the balance of mitosis and apoptosis equal?

A

Homeostasis

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4
Q

In what physiologic state is the rate of mitosis too high compared to apoptosis?

A

Neoplasia

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5
Q

In what physiologic state is the rate of apoptosis too high compared to mitosis?

A

Degeneration

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6
Q

What is the difference between apoptosis and necrosis?

A

Apoptosis is a “clean” cell death

necrosis is cell death with inflammation

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7
Q

Describe the steps of apoptosis

A

Cell shrinks
Cell breaks down in to apoptotic bodies
Apoptotic bodies are phagocytosed by neighboring cells

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8
Q

Does apoptosis induce inflammation?

A

No

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9
Q

Describe the steps of necrosis

A

Cell swells

Plasma membrane of cell breaks and contents flow out

Cell is lysed

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10
Q

What are the 4 death triggers of apoptosis?

A

Death triggers:
Lack of survival factors, growth factors or hormones

DNA damage

Death ligands and receptors

Oxidative stress

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11
Q

What enzyme is used for the initiation of the death receptor pathway?

A

Capase 8

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12
Q

What enzyme is used for the initiation of the mitochondrial pathway?

A

Capase 9

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13
Q

Describe the execution stage of apoptosis

A

Integration capases (8,9) activate capases 3,6 and 7

Capase 3,6,7 activate proteases and endonucleases that cleave cytoskeleton and DNA, respectively

Cleavage of cytoskeleton and DNA leaves fragments tagged for phagocytosis by macrophages

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14
Q

What is the chopping machine of the apoptosis pathway?

A

Capase 3,6,7

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15
Q

Describe the Fas-FasL Death receptor pathway

A

Fas ligand binds to Fas receptor and associates with Fas Associated Death Domain and procapase 8 to form the Death Inducing Signaling complex

Capase 8 is released from DISC

Capase 8 activates capase 3,6,7 to execute apoptosis

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16
Q

Describe the mitochondrial death pathway via Bax

A

Fas ligand binds to Fas receptor and associates with Fas Associated Death Domain and procapase 8 to form the Death Inducing Signaling complex

Capase 8 is released from DISC

Capase 8 activates capase 3,6,7 to execute apoptosis

Transcription of Bax: apoptosis signaling molecule

Bax enters creates pore in mitochondrial membrane

cytochrome c enters cytoplasm and associates with apoptosis protease activating factor and procapase 9

Capase 9 is released from apoptosome

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17
Q

What leads to transcription of p53?

A

Moderate cell damage

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18
Q

What is the function of p53?

A

Tumor suppressor

Induction of Bax transcription

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19
Q

How is apoptosis associated with bcl2?

A

bcl2 is an anti-apoptotic molecule

20
Q

What 3 functions does the Fas-FasL pathway participate in?

A

Inflammation
Termination of immune response (autocrine suicide T-cells)
Cancer cells express FasL to promote cytotoxic T-cells

21
Q

What is autocrine suicide & juxtracrine fratricide?

A

During inflammatory conditions, cells express FasL which causes autocrine suicide or juxtracrine fraticide

22
Q

Describe the pathway of juxtracrine fraticide

A

DISC complex forms on cell

Capase 8 is activated and FasL is activated to go to adjacent cell

23
Q

How does failure of the FasL-Fas system lead to autoimmune diseases?

A

Lymphocytes fail to die

Rampant Ab production

24
Q

What is a proto-oncogene?

A

Genes that code for the signaling of molecules that are involved in regulation of cell growth and prevention of apoptosis

25
Q

What are oncogenes?

A

Mutated or overexpressed proto-oncogenes

Cause cancer

26
Q

What causes the mutation of proto-oncogenes to oncogenes?

A

Spontaneous development

Retro-viruses

27
Q

Name 2 tumor suppressor genes

A

p53, pRB

28
Q

Describe how the accumulation of multiple mutations leads to cancer

A

Loss of 2 plasma-membrane bound signaling molecules

Mutation of ras (cell growth gene) leads to alternative cell growth

Alternative cell growth forms adenoma

2 more plasma-membrane signaling molecules are lost

More proliferation of alternative cells

homozygous loss of p53

Invasive carcinoma

29
Q

Why is the proto-oncogene RAS important?

A

Intrinsic GTPase activity turns RAS (transcription) off

30
Q

What happens if the proto-oncogene RAS is mutated to the oncogene RAS

A

oncogene RAS lacks GTPase activity

Cannot terminate proliferation signals

Cancer

31
Q

What is the function of p53 on a cell with minor damage? Major damage?

A

If damage was minor, p53 halts cell cycle until DNA is repaired

If damage was major, p53 halts cell cycle and induces apoptosis via BAX

32
Q

What is the result of p53 being inhibited?

A

Cell cycle does not halt and damaged DNA is proliferated

May cause carcinomas

33
Q

Name the growth factor oncogene. Type of cancer?

A

sis, human cancer

34
Q

Name the growth factor receptor oncogene. Type of cancer?

A

erb B, canine mammary carcinomas

35
Q

name the signal transduction protein oncogene. Type of cancer?

A

ras, src

many cancers

36
Q

Name the nuclear transcription factor oncogene. Type of cancer?

A

myc, jun, fos

Human and animal cancers

37
Q

Name the cell cycle regulator oncogene. Type of cancer?

A

Cyclin D

Breast cancer

38
Q

Name the tumor suppressor gene oncogenes. Type of cancers?

A

pRB, p53
Retinoblastomas
Osteosarcomas

39
Q

Name the anti-apoptosis oncogene. Type of cancer?

A

bcl-2

Leukemia

40
Q

Which oncogenes were discovered due to their presence in retoviruses?

A

sis, erb B, ras, src, myc, fos, jun

41
Q

Retroviruses cause the transformation of cells. Why is this important in cancer?

A

Normal cells inhibit growth after contacting neighboring cells

Transformed cells do not inhibit growth after contacting neighboring cells

42
Q

What is unique about retroviruses?

A

Reverse transcription (DNA from RNA)

43
Q

Describe how retroviruses infect hosts

A

Viruses binds to membrane and capsid is endocytosed

Capsid dissolves and viral RNA is transcribed into viral DNA

viral DNA is integrated in to host’s DNA

host genome will transcribe and translate viral RNA

viral RNA is assembled in to a capsid enveloped in transcribed viral envelopes are exocytosed by the cell

44
Q

What is the rous sarcoma virus?

A

Virus carries large portion of host genome and relies on helper viruses for own replication

If passenger gene is an oncogene, can cause cancer

45
Q

Describe how a virus containing the oncogene RAS would cause cancer

A

Viral RNA is transcribed to DNA

Oncogene RAS is transcribed

Oncogene RAS cannot turn off cell signal proliferation

Physiology (45 decks)

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