Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

YR2: MCD Cancer > Signalling Mechanisms in Growth and Division > Flashcards

Signalling Mechanisms in Growth and Division Flashcards

1
Q

What transcription factor is stimulated by growth factor signalling and is vital to starting the cell cycle?

A

c-Myc

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Describe what happens to tyrosine kinase receptors when growth factors bind to them.

A

TK receptors are usually present on membranes as monomers
Most GFs are dimers, so on binding, they bring TK receptors close together
Allows TK receptors to cross-phosphorylate (using gamma phosphate from ATP to phosphorylate tyrosine residues in proteins)
Phosphorylated domains on TK receptors act as docking sites for adaptor proteins

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

Give an example of an anti-cancer drug that targets tyrosine kinase receptors.

A

Herceptin
Inhibits HER2 TK receptor (important in many tumours e.g. breast)
Prevents ligand binding + subsequent signalling

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Name an important adaptor protein.

A

Grb2

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

Describe the structure of Grb2.

A

Modular
SH2 domain: binds to docking sites
2 SH3 domains: bind to proline-rich regions of proteins

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Describe how receptor protein tyrosine kinases can signal to Ras.

A

Grb2 is constituently bound to an exchange factor: Sos
When TK receptors become active + docking sites become available, Grb2 binds to the docking site
This brings Sos close enough to the membrane + Ras, to allow it to exchange the GDP on Ras for GTP
GTP bound Ras is active

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

What must the Ras protein be bound to for it to become activated?

A

Plasma membrane

Interference with membrane binding of Ras can make a good anti-cancer drug

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

How is Ras turned on and off?

A

On: Exchange factors e.g. Sos exchange GDP on Ras to GTP

Ras has intrinsic GTP hydrolysis capability: GTPase activity is stimulated by GTPase-activating proteins (GAPs)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Broadly speaking, how might Ras signalling be different in cancer?

A

Ras could be permanently switched on (GTP bound form), thus it constantly signals cell division

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Describe two mutations that lead to an increase in the amount of active Ras.

A

V21Ras: glycine replaced by valine. Prevents GAP binding Ras, thus prevents inactivation of Ras.
L61Ras: glutamine replaced by leucine. Prevents GTP hydrolysis so Ras remains in the active, GTP bound form.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

What cascade does Ras activate?

A

ERK cascade (Extracellular signal-regulated kinase cascade)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

What is the family that the ERK cascade belongs to called?

A

MAPK cascade (Mitogen-activated protein kinase cascade)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

What are the three kinases involved in the ERK cascade?

A

Raf (MAPKKK)
MEK (MAPKK)
ERK (MAPK)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

What does the last kinase in the cascade phosphorylate?

A

Gene regulatory proteins (transcription factors e.g. c-Myc), which go on to regulate the expression of genes
Also phosphorylates other proteins + change their activity

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

What are c-Myc and Ras classed as? What would mutation in either result in?

A

Oncogenes

Mutation causes Cancer

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

What type of kinase are cyclin-dependent kinases (Cdks)?

A

Serine-threonine kinases

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

What conditions do Cdks require to become activated?

A

Binding to cyclin
Phosphorylation (activating phosphorylation + removal of inhibitory phosphorylation)
(+ degradation of Cdk inhibitors)

18
Q

What does the mitosis-promoting factor (MPF) consist of?

A

Cdk1 + cyclin B

19
Q

What are the requirements, in terms of phosphorylation, for MPF to become active?

A

Activating phosphorylation by CAK (Cdk activating kinase)

Removal of the inhibitory phosphorylation (that was placed by Wee1) by Cdc25 phosphatase

20
Q

What activates MPF at the end of interphase?

A

Removal of the inhibitory phosphorylation by Cdc25 phosphatase

21
Q

Describe the positive feedback loop that is formed by MPF activation.

A

Removal of the inhibitory phosphorylation by Cdc25 produces active MPF, which then phosphorylates Cdc25 + increases its activity meaning that more MPF can be activated

22
Q

How does MPF put mitosis on hold before progressing to the next stage?

A

At end of metaphase, it phosphorylates key substrates + inhibits their action (thus putting mitosis on hold)
Signal from fully attached kinetochores causes cyclin B degradation, Cdk1 is inactivated + the substrates become dephosphorylated + hence active.

23
Q

Which Cdk/cyclin is required for G1/S phase?

A

Cdk2-cyclin E

24
Q

Which Cdk/cyclin is required for S phase?

A

Cdk2-cyclin A

25
Q

How can the same Cdk be used for two different stages?

A

Cyclin binding alters the substrate specificity of Cdk

Also, substrate availability changes throughout cell cycle

26
Q

What is one of the most important transcription targets of c-Myc? What does this do?

A

Cyclin D

Stimulates transcription of other genes

27
Q

What is the first Cdk/cyclin complex that is formed when a cell goes from G0 to G1?

A

Cdk4/6-cyclin D

28
Q

The Cdk4/6-cyclin D complex then stimulates the expression of the next cyclin in the cell cycle. What properties does this system give to the cell cycle?

A

Gives cell cycle direction + timing (because Cdk-cyclin complexes must reach a certain concentration before they can trigger the next stage)

29
Q

Give an example of a phosphorylation target of MPF that allows the cell cycle to progress.

A

Phosphorylation of nuclear lamins allows breakdown of the nuclear envelope

30
Q

What is start kinase and what is one of its most important targets?

A

Start kinase = Cdk2-cyclin E

Retinoblastoma protein

31
Q

Describe the role of retinoblastoma in the quiescent G0 state.

A

Retinoblastoma is unphosphorylated

It binds to + sequesters a group of transcription factors: E2F

32
Q

What effect does Cdk4/6-cyclin D have on retinoblastoma?

A

It multiply phosphorylates retinoblastoma
On phosphorylation it loses its affinity for E2F + releases E2F
E2F transcription factors regulate gene expression + promote progression of the cell cycle

33
Q

What is one of the main targets of E2F?

A

Cyclin E (the next cyclin in the cell cycle)

34
Q

What type of gene is retinoblastoma?

A

Tumour suppressor gene (acts a brake on the cell cycle)

35
Q

State some important genes that are regulated by E2F.

A

Proto-oncogenes: c-Myc, n-Myc
Cell cycle: E2F-1,2,3, pRb, cyclin A, cyclin E, CDK4, CDK2
DNA synthesis: thymidine kinase, thymidine synthetase, dihydrofolate reductase, DNA polymerase

36
Q

The initial release of E2F allows transcription of cyclin E leading to the formation of Cdk2-cyclin E. What effect does this complex have on retinoblastoma?

A

Cdk2-cyclin E further phosphorylates retinoblastoma so more E2F is released + conc. of E2F increases

37
Q

What is the significance of the increasing concentration of E2F?

A

E2F can now bind to targets with a lower affinity (e.g. cyclin A gene promoter isn’t activated until the E2F concentration is high enough)

38
Q

What are the 2 families of Cdk inhibitors?

A

INK4

CIP/KIP

39
Q

During which phase do each of the families act and how do they inhibit Cdk?

A

INK4: G1 phase: displaces cyclin D from Cdk4/6-cyclin D complex
CIP/KIP: S phase: binds to Cdk/cyclin complexes + inhibits them
These inhibitors need to be degraded at various stages for the cell cycle to progress

40
Q

State 5 common and important oncogenes.

A

EGFR/HER2: mutationally activated or over-expressed in many breast cancers
Ras: mutationally activated in many cancers
Cyclin D1: overexpressed in 50% of breast cancers
B-Raf: mutationally activated in melanomas
c-Myc: overexpressed in many tumours

41
Q

State 2 important tumour suppressor genes.

A

Rb: inactivated in many cancers
p27KIP1: under-expression correlates with poor prognosis in many malignancies

42
Q

Describe the presence of Cyclins in the cell cycle

A

Transiently expressed at specific points
Regulated at level of expression
Synthesised then degraded quickly

YR2: MCD Cancer (18 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions