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Bio 361 - Molecular Genome and Genomics > Midterm 2 - Notes 4 (Part 3) > Flashcards

Midterm 2 - Notes 4 (Part 3) Flashcards

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1
Q

What does Ras do in its natural form? (2)

A
  1. It helps regulate entry into the S phase

2. Monitor GTPase

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2
Q

What is Ras involved with?

A

Cell cycle control

- entry into the S phase

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3
Q

What does Ras encode?

A

A small GTP binding protein called GTPase

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4
Q

What is Ras activated by?

A

GEF

- turns on

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5
Q

GEF

A

Guanine nucleotide exchange factor

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6
Q

What does GEF lead to?

A

Activation of downstream signalling components

- eg) MAP Kinase

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7
Q

What is Ras inactivated by?

A

GAPs

- turns off

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8
Q

GAP

A

GTPase activating enzyme

- enhance intrinsic GTPase activity

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9
Q

What can happen when Ras is mutated?

A

It can stay active and create mutations

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10
Q

What activates Ras?

A

A mitogen

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11
Q

What does Ras initiate?

A

MAP kinase cascade

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12
Q

MAPK

A

Mitogen activated protein kinase

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13
Q

What does Ras activates?

A

MAP kinase kinase kinase

  • phosphorylates MAP kinase kinase
  • phosphorylates MAP kinase
  • phosphorylates target proteins like TF
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14
Q

What is used to help activate proteins?

A

ATP

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15
Q

Can you phosphorylate more then 1 protein?

A

Yes

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16
Q

What do you get through a kinase type cascade?

A

Strong amplification

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17
Q

What does phosphorylation allow?

A

Cross connection (activation)

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18
Q

What are the 6 steps in Ras activation?

A
  1. Ras activated by exchange of GDP for GTP
  2. Active Ras recruits, binds and activates Raf
  3. GTP hydrolysis leads to dissociation of Ras from Raf
  4. Raf activates MEK
  5. MEK activates MAPK
  6. Dimeric form of MAPK translocates to the nucleus
    - activates many TF
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19
Q

In the S-phase activation pathway what does binding of a mitogen to a cell surface receptor lead to?

A

Activation of a specific GEF which leads to the activation of Ras

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20
Q

What does activated Ras initiate?

A

MAPK cascade

21
Q

What does activated MAPK phosphorylate?

A

TF

22
Q

What does Myc activates?

A

Transcription of delayed response genes

23
Q

What is an example of a delayed response gene?

A

G1/S cyclins

24
Q

What do cyclins bind to?

A

CDK

25
Q

CDK

A

Cyclin dependent kinase

26
Q

What complex phosphorylates Rb?

A

G1/CDK

27
Q

What is p53?

A

A famous proto oncogene

28
Q

Where is mutated p53 most commonly found?

A

Many types of cancer

29
Q

Is p53 essential for development?

A

No

- homozygous null mutations (in a mouse) appear normal

30
Q

What makes amounts of p53 increase?

A

Stress

31
Q

What are 2 examples of stresses that can increase amount of p53 and cause damage?

A
  1. UV radiation

2. X-rays

32
Q

What are 4 kinds of signals that come from tumour cells?

A
  1. Hyper-proliferation signals
  2. DNA damage
  3. Telomere shortening
  4. Hypoxia
33
Q

What is a hallmark of tumour formation?

A

Hypoxia

34
Q

What is p53’s primary role?

A

Prevention of cancer

  • is a tumour suppressor gene
  • its a TF
35
Q

Where are most cancerous LOF mutations located?

A

In DNA binding domains

- when mutated it prevents it to bind to its target gene and acts as a regulatory gene

36
Q

What does DNA damage induce?

A

Kinase cascade

37
Q

What happens when p53 is phosphorylated?

A

It gets activated

38
Q

What is produced in high levels?

A

p53

- as long as there is no signal that activates the protein we get binding

39
Q

What is one target of p53 transcriptional activation?

A

p21 protein

40
Q

What does high turn over rate for p53 lead to?

A

Leads to little p53 present (in a steady state) in the cell because it is degraded very quickly

41
Q

What does p21 bind to?

A

G1/S phase activated cyclin dependent kinase

- G1/S-CDK

42
Q

What happens when p21 bind to G1/S-CDK?

A

It inactivates it

43
Q

What does phosphorylation of p53 prevent?

A

Prevents binding of p53 to Mdm2

44
Q

What happens when p53 is bound to Mdm2?

A

It is targeted for degradation

45
Q

When is p53 a stable protein?

A

When it is not bound to Mdm2

46
Q

What happens when Mdm2 is no longer bound to p53?

A

It is able to proceed with transcription

47
Q

What can p21 engage in?

A

Protein protein interaction

  • can bind to CDK
  • this inactivates it
48
Q

What happens if DNA is damaged?

A

It cant enter into the S-phase

Bio 361 - Molecular Genome and Genomics (35 decks)

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