Give an example of a Class 1 Onocgene- Growth Factors
Erb-B
ERK
Sis
What is the function of the sis protein?
Forms a PDGF(Beta) chain
Forms a IPGF(Beta) chain
Forms a IGF1(Beta) chain
Name the two ways a cell can access extra Growth factor
A virus produces extra growth factor as it replicates
A cell begins to make it's own growth factor through growth factor genes
A cell begins to steal growth factor from surrounding cells
Name the Class 2 oncogene
Growth Factor Receptors
Growth Factors
Intracellular Transducers
Name a Class 2 Oncogene
IGF1
TGFB
How does Erb-b become oncogene?
....bind permanently to their ligand and so become constitutionally active
... no longer need their ligand to activate become constitutionally active
...form a constitutionally active dimer
...no longer needs to dimerise to activate
What is erb-b?
Family of tyrosine kinase receptors that bind to EGF
Family of tyrosine kinase receptors that bind to TGFB
Family of tyrosine kinase receptors that bind to IGF1
Similarly, in 'neu' receptors, what replaces the Valine to make a constantly active receptor?
Glutamine
Glutamic Acid
Glutamate
What is Herceptin?
A tyrosine kinase agonist?
A humanised monoclonal antibody
An Erb-B agonist
What does Herceptin bind to?
Erb B
HER2
Tyrosine Kinase
Name the 3rd Class of Oncogenes
Growth factors
Transcription factors
Intracellular transducers
Which of the following is a class 3A oncogoene?
Src
c-myc
What determines the types of src tyrosine kinase present in the cell?
The cell type
The stage of the cell cycle
The age of the cycle
What is the role of Cellular Transducers
Relay information to the nucleus to regulate gene transcription
Relay information to the ribosomes to regulate protein synthesis
Relay information to the Golgi Complex to regulate cell receptor production
What allows Src to stick to the cytoplasm
A modified lipid
A modified glycoprotein
A modified phospholipid
Name the substance that anchors src to the membrane
Myristate
Palmatite
Acetylate
What holds src kinase shut in its inactive form?
A phosphate on Tyr 527 in its inactive form & the SH2 domain
A phosphate on Tyr 527 in its inactive form & the SH3 domain
A phosphate on Tyr 537 in its inactive form & the SH2 domain
Put the following domains of Src in order A- Unique Domain B- Sh2 Domain C-Catalytic Domain D- Regulatory Domain E- SH3
A-B-E-C-D
A-B-C-D-E
A-B-D-E-C
What is the focus of an SH3 domain?
Protein- protein interaction
Protein- phosphotyrosine interaction
Protein-phosphoserine interactoin
What sequence is favored by SH3 domains?
Proline rich; Pro-X-X-Pro
Histadine rich; His-X-X-His
Gycine rich; Gy-X-X-Gly
What is required for Src to activate?
For the protein to be at the membrane
For the protein to be cytosolic
The SH2 domain then releases the regulatory domain and binds to P-Tyrosine Kinase
What happens to the regulatory domain once the SH2 domain has released it?
It's dephosphorylated by a phosphatase at the membrane at Tyr 527
It's phosphorylated by the tyrosine kinase at Tyr 527
Nothing
What tyrosine residue is phosphorylated by tyrosine kinase?
416 on the activation lip
417 on the activation lip
418 on the activation lip
What is the most common oncogene form of src?
Loss of regulatory domain (last 19 amino acids) so it cannot be phosphorylated
Loss of SH2 domain so it cannot bind to regulatory domain when phosphorylated
Modified lipid binds permanently to the membrane
Ras is the name of a small family of what?
GTPase's
ATPase's
UTPase's
What process localyses Ras to the membrane?
Acetylation
Methylation
Farnesylation
What is sos?
A GAP
A GEF
A GDI
Where does GTP bind to ras?
At the C and N terminus
In the centre
What is the purpose of the discrete domain of Ras
To bind GTP
To bind GDP
To bind downstream molecules
What are GDI's?
Guanine Nucleotide Disassociation Inhibitors
Guanine Nucleotide Dimerisation Inhibitors
Gunanine Nucleotide Decamerisation Inhibitors
What is the purpose of a GDI and how it controlled?
By molecules recruited to the tyrosine receptor
Bind to Ras and prevent activation
Bind to Ras and prevent de-activation
In which domains can a single mutation turn Ras into an oncogene?
L1
L2
L3
L4
L5
What is the role of GRB2
Binds Ras to membrane
Binds Ras to TK receptor
Binds Ras to Raf
How many SH2 domains does GRB2 have?
2- both in the middle
2- one on each end
1 in the middle
1 at the N terminus
1 at the C terminus
What protein is used by Src to activate Ras?
Srk
Sch
Shc
How does src phosphorylate the protein that activates Ras?
Binds to SH3 domain
Binds to SH2 domain
Binds to discrete domain
Name the two proteins for which phosphorylated Shc has a very high affinity?
Ras
Sos
GRB2
GDI
Name the 4th class of oncogenes
Cellular Transporters
Name a class 4 oncogene
Jun
Name the part of c-jun that causes dimerisation
Leu Zipper
His zipper
Ala zipper
Where is the unique sequence of c-jun and what is it's role?
Near the center
Near the c-terminus
Near the n-terminus
Defines family member
Determines where in the DNA c-jun binds
Put the domains of C-jun in the correct order A-Leu Zipper B- Delta Domain C-Transcription Domain D- Unique Domain E- DNA Binding Domain
D-B-C-E-A
D-E-A-B-C
C-A-D-B-E
How does C-jun function
As a homodimer
As a heterodimer
As both
What is the first step of c-jun homodimer activation?
Dephosphorylation by PKC
Phosphorylation by JNK (ERK parallel protein)
What is the second step of c-jun homodimer activation?
Dephosphorylation by PKB
Phosphorylation by JNK
What part(s) of c-jun is lost to make it an oncogene?
Unique sequence
Delta Domain
Leu zipper
Name a protein likely to form a heterodimer with c-jun
AFK
AFT
AFR
What tends to be transcribed by the first c-jun heterodimer to form?
c-jun
Fos
What is the second protein to heterodimerise with c-jun?
Fas
Fis
What is the name of the second heterodimer formed by c-jun?
AP1
Ap2
AP
What is required for Fos transcription?
TCF/AFK to be activated by ERK
AFK to be activated by ERK
TCF to be activated by ERK
What sequences does AP1 bind to?
TGAC
GTAC
GGAC
What is transcribed by AP1?
Ribosomal proteins
Is Cyclin D1 transcribed by Jun?
Yes
No
What happens if the signal activating AP1 persists for 30 mins?
It's activity is increased further by phosphorylation
It's activity is increased further by methylation
By Jnk/Erk
What transcribes C-Myc?
API
c-Jun
How long is the half life of C-myc?
5-10 mins
5-10 seconds
3-5 mins
What does Myc bind to in order to interact with E-Box sequences?
Max
Mad
Mac
Why is Ubiquitin ligase transcribed by c-myc?
Halts protein turnover & allows protein levels to build up
Increases protein turnover so only new proteins are involved in the cell cycle
In normal cells, which of the following is in excess, and why?
Max, so the dimer only forms when Myc levels are signaled to rise
Mic, so the dimer only forms when Max levels are signalled to rise
How are Max homodimers inhibitory?
They block jun transcription sites
They block jun expression promoters
They block myc expression promoters
What is different in tumor cells from normal cells (concerning myc/max levels)?
Myc levels are always higher than Max
Max levels are always higher than myc
