Brainscape's Knowledge GenomeTM


Top Flashcards (Certified)
All Flashcards

MCD Cancer > Signalling mechanisms of growth and division > Flashcards

Signalling mechanisms of growth and division Flashcards

1
Q

In what phase are most adult cells?

A

G0 (quiescent phase)

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

What is the role of c-Myc?

A

Transcription factor that stimulates expression of cell cycle genes

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

What are Myc conc levels like during the quiescent G0 phase and when cell division is triggered?

A

Very low in G0 phase but rapid increase in Myc when cell division is triggered which then plateaus at an intermediate level- this correlates with cells moving out of G0 and into G1

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

What stimulates the cell cycle by signalling pathways?

A

Growth factor

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

What sort of receptor does growth factor usually bind to?

A

Tyrosine kinase type receptors

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

What does growth factor act via after binding to the receptor?

A

Small GTP-binding protein - Ras

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

What does Ras trigger?

A

Kinase cascade

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

How quick is the early stage of the cell cycle triggering?

A

Very fast

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

What does the kinase cascade trigger?

A

Activation of genes that are required for the progression of cells through the cell cycle

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

How does the speed of the gene activation compare to the earlier stage of the cell cycle triggering?

A

It is slower because it requires transcription and translation to take place

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

What is an example of a mitogenic growth factor?

A

Hepatocyte growth factor

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

What does the phosphorylated receptor protein tyrosine kinase recruit?

A

Adapter and signalling proteins (Grb2)

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

What sort of receptors normally sit on the plasma membrane in terms of oligomerisation?

A

Monomers

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

What are most growth factors in terms of oligomerisation?

A

Dimers

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

What happens when the dimeric growth factor binds to the two receptor tyrosine kinase molecules?

A

It brings them closer together

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

What is able to happen when the two receptors are close together?

A

The tyrosine kinase domain is able to cross-phosphorylate the partner receptor

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

What do the tyrosine kinases use to phosphorylate the tyrosine residues in proteins?

A

Gamma phosphate of ATP

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

What do the phosphorylated domains on the tyrosine kinase receptors act as?

A

Docking sites for adaptor proteins which contribute to downstream signalling

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

What does the antibody herceptin do?

A

Inhibits the her2 receptor tyrosine kinase

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

Why is herceptin’s function important?

A

It can be used to treat a number of tumours- it blocks the early stage of growth stimulation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

What is one of the important adaptor molecules that is recruited?

A

Grb2

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

What does the fact that adaptor proteins are often modular mean?

A

There are different domains that are mixed and matched to give the protein different properties which are important in molecular recognition

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

What other roles do adaptor proteins have apart from binging proteins together?

A

None! No enzymatic activity

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

What are the only two types of Grb protein-protein interactions?

A

SH2- binds to phosphorylated tyrosine of the receptor

SH3 (two copies)- binds to the proline rich regions of other proteins

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
What else does Grb bind to as well as RPTK via its SH2 domain?
A protein called Sos through its SH3 domains (Grb is always bound to Sos)
26
What is Sos?
An exchange factor for Ras (a signalling molecule that sits in the membrane of the cell)
27
When RPTK becomes activated, what happens?
Phosphorylation of the receptor
28
What happens after phosphorylation of the receptor?
Grb2 (with Sos attached) binds to the phosphorylated tyrosine domains and Sos is then close enough to the membrane to activate Ras
29
How does Sos activate Ras?
It allows the exchange of GDP for GTP in Ras to form a GTP bound form of Ras- this changes the conformation of Ras which puts it into an active state that can signal downstream and can allow the propagation of the signal
30
For Ras to work, what has to happen and how is this information used clinically?
It has to bind with the plasma membrane | Interfering with the membrane binding of the Ras, you can make good anti-cancer therapy
31
What sort of protein is Ras?
GTP binding proteins
32
What are GTP binding proteins very effective at?
Being molecular switches: On- GTP bound Off- GDP bound
33
Why is GTP replacing GDP to make Ras active not phosphorylation?
It is merely an exchange of GDP for GTP (catalysed by Sos)
34
What is intrinsic GTP hydrolysis capability?
The GTP binding protein is able to hydrolyse GTP to GDP to turn itself off
35
What else can stimulate the hydrolysis of the GTP?
GTPase activating proteins (GAPs)
36
What is the cycle of GTP binding proteins almost always controlled by?
Turn it on: Exchange factors (e.g. Sos) | Turn it off: GTPase activating proteins (GAPs)
37
What is the main G-protein in case of growth factor stimulatory pathways?
Ras
38
Why is it very important that you are able to turn off the signalling activity of Ras protein?
Prevent uncontrolled division- Ras is mutated in ways that cause the Ras protein to constantly be in the GTP bound form
39
What is V12Ras?
Glycine residue in position 12 of the Ras protein has changed to valine due to a Ras gene mutation- side chain has gone from being a simple hydrogen (in glycine) to a hydrophobic side chain (valine)
40
What effect does the change in structure between Ras and V12Ras have?
It prevents GAPs from binding to Ras thus meaning that Ras can't turn off very easily
41
What is L61Ras?
Glutamine in position 61 is converted to leucine- single base change in the genome- side chain goes from being an amide to a hydrophobic side chain
42
What effect does the change in structure between Ras and L61Ras have?
It inhibits the intrinsic GTPase activity of the Ras protein so it ends up being constantly in the GTP bound state and giving growth stimulatory signals
43
What does Ras activate?
Protein kinase cascade
44
How does the protein kinase cascade work?
GTP bound Ras binds to a kinase and then that kinase activates several other kinases etc
45
What is the kinase cascade that is involved in growth stimulatory signalling known as?
ERK cascade (extracellular signal-regulated kinase cascade)
46
What is the name of this family of kinase cascades?
MAPK cascades (mitogen-activated protein kinase cascade)
47
What are the three kinases specific to ERK in order?
Raf MEK EPK
48
What do protein kinases do?
Stimulate changes in cell proteins and gene expression to promote division
49
What does the last kinase (EPK) of the cascade do?
Phosphorylates a number of proteins and changes their activity including gene regulatory proteins (transcription factors) which then go on to regulate gene expression
50
What effect does activating the growth factor pathway have on c-Myc production?
The kinase cascade leads to activation of a gene regulatory protein which stimulates c-Myc production as it is a key molecule in stimulating growth
51
What sort of genes are Myc and Ras?
Oncogenes
52
What is cell cycle control based on?
Cyclically activated protein kinases
53
What does Cdk stand for?
Cyclin-dependent kinase
54
What sort of kinase are Cdks?
Serine-threonine kinases
55
Where are Cdks found?
Present in proliferating cells throughout cell cycle
56
What is Cdk activity regulated by?
Interaction with cyclins to become activated and phosphorylation
57
Where are cyclins found?
They are transiently expressed at specific points in the cell cycle
58
What happens to cyclins after they've activated Cdks?
Cyclins are degraded
59
What are cyclins regulated by?
Level of expression
60
Why are there different cyclin-cdk complexes?
They trigger different effects in the cell cycle
61
What controls the progression through mitosis?
M-phase promoting factor
62
What turns on the Cdk at the start of DNA replication?
An S phase cyclin binding
63
What does the mitosis promoting factor consist of?
Cdk1 and mitotic cyclin (usually cyclin B)
64
What does Cdk1 bind to?
Cyclin B
65
In what state is the Cdk1-cyclin B complex normally?
Inactive on its own
66
What is the other level of regulation of Cdk-cyclin complexes?
Phosphorylation- there are 2 phosphorylation reactions | Cdk has to be activated at specific sites
67
What performs the activation of Cdk?
Cdk activating kinase (CAK)
68
What puts an inhibitory phosphorylation on Cdk1 and opposes the action of CAK?
Wee1- an inhibitory kinase
69
What removes the inhibitory phosphate that Wee1 puts on hence allowing Cdk1 to function?
Cdc25
70
Give an overview of the steps involved in activating MPF
Cyclin binding to Cdk Activating phosphorylation by CAK Removal of inhibitory phosphate (put on by Wee1) by Cdc25
71
When does the dephosphorylation that activates Cdk1 occur?
At the end of interphase
72
What effect does active MPF have on Cdc25?
It can phosphorylate it to upregulate its activity- positive feedback
73
What does MPF do when active at the end of metaphase?
Phosphorylates a number of key substrates that are involved in the mitotic process
74
What effect does MPF phosphorylating the key substrates involved in mitosis have?
It puts mitosis on hold- they can't progress to the next stage until a signal is sent saying that metaphase has been achieved
75
What happens once metaphase has been achieved and the kinetochores are correctly attached to the microtubule spindles?
A signal is released that causes cyclin B to be degraded which means Cdk1 becomes inactive so the substrates keeping mitosis on hold are dephosphorylated so mitosis can then progress
76
What Cdks and cyclins are involved in G1/S phase?
Cdk2 | Cyclin E
77
What Cdks and cyclins are involved in just S phase?
Cdk2 | Cyclin A
78
Even though Cdk2 is involved in G1 and S phase, why does it carry out different jobs in both?
When cyclin binds to cdk it actually changes its substrate specificity so it can phosphorylate different substrates depending on which cyclins are bound to it. It also changes substrate accessibility
79
What does cyclin D activate and what does that stimulate?
Cdk4 and Cdk6 which stimulates synthesis of cyclin E
80
What effect does each cyclin being involved with stimulating the synthesis of the next cyclin have?
It gives direction to the cell cycle and gives timing because it takes time for the concentration of cyclin to build up so appropriate Cdk is activated
81
What do Cdks do?
Phosphorylate proteins to drive cell cycle progression
82
What causes breakdown of the nuclear envelope?
Phosphorylation of nuclear laming by MPF
83
What is the start kinase?
(From G1 to S)- complex of Cdk2 and G1 cyclin (Cyclin E)- phosphorylates substrates needed for that phase
84
What is the most important protein that is phosphorylated by start kinase?
Retinoblastoma- key protein in regulating cell cycle (present throughout)
85
In the G0 resting state, what is retinoblastoma like and what does it do?
Unphosphorylated | It binds to and sequesters a family of transcription factors called E2F
86
What happens when E2F transcription factors are held in the cytoplasm by unphosphorylated retinoblastoma?
Everything is turned off
87
What is retinoblastoma protein a target for?
Cdk4/6-cyclin D kinase (which becomes active following Myc induction)
88
What effect does Cdk4/6-cyclin D kinase have on retinoblastoma?
It phosphorylates retinoblastoma and as it becomes phosphorylated it loses affinity for E2F so releases E2F
89
What does E2F transcription factors do after being released?
Bind to promoters in the nucleus of genes that are involved in cell cycle progression
90
What is one of the main targets for E2F transcription factors?
Gene for cyclin E- next cyclin required for cell cycle progression
91
What do retinoblastoma act as in the cell cycle?
A brake- when it's unphosphorylated, it sequesters the E2F transcription factors and prevents gene expression needed for progression
92
What sort of gene is retinoblastoma?
Tumour supressor gene
93
What is retinoblastoma like in tumour cells?
Many tumour cells have reduced levels of retinoblastoma so it can't regulate E2F activity so it progresses through cell cycle in an uncontrolled manner
94
What genes are regulated by E2F transcription factors?
Protooncogenes (including Myc) Involved in the S phase e.g. thymidine kinase Involved in the cell cycle e.g. cyclin A and E (first target)
95
What does Myc do?
Turns on cyclin D which complexes with Cdk4/6
96
What does the Cdk4/6 complex do?
Phosphorylates retinoblastoma and allows E2F to start being released in the cytoplasm which stimulates the production of cyclin E
97
What does cyclin E form and what does that do?
Forms a complex with Cdk2 and this complex then further phosphorylates retinoblastoma leading to a further increase in E2F
98
What does the increase in E2F concentration caused by cyclin E mean?
It can now bind to targets with lower affinity
99
Until what is the cyclin A gene promoter not activated?
Until the E2F concentration is high enough
100
What regulates Cdks?
Cdk inhibitors
101
What are the two Cdk inhibitor families and when are they found?
INK4 family- active in G1 | CIP/KIP family- active in S phase
102
How do the INK4 and CIP families work?
INK4- inhibits Cdk4/6 by displacing cyclin D | CIP/KIP- inhibits the Cdk/cyclin complexes by binding to it
103
Which genes are commonly over expressed/produced and lost
Lost- Tumour supressor | More- Oncogenes
104
What cell cycle oncogenes are there?
``` Cell surface tyrosine kinase receptors- EGFR/HER2 Ras Cyclin D1 B-Raf c-Myc ```
105
What cell cycle tumour suppressors are there?
Rb | p27KIP1

MCD Cancer (15 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2025 Bold Learning Solutions. Terms and Conditions