Lecture 15 (nuclear oncoproteins) Flashcards
Examples of nuclear oncoproteins
Jun, Fos, ATF, Maf, CREB
What is the viral ErbA oncogene?
A gag fusion protein
What is ErbA?
Thyroid hormone receptor
What does ErbA do?
Blocks differentiation of erythroblasts to erythrocytes
Does ErbA cause transformation?
Not by itself, but it enhances the ability of ErbB to cause transformation
Can the ErbA oncogene still bind the thyroid response element?
Yes, but has lost the ability to bind the thyroid hormone
ErbA has sequence homology to…
steroid hormone receptors (particularly DNA binding region)
Jun oncogene was isolated in __
ASV-17 virus
Fos oncogene was isolated in __
FBJ-MuSV
What transcriptional regulator do both jun and fos show sequence homology to?
GCN4
Jun and Fos form a complex which binds DNA called the __ complex
AP-1
What region of the AP-1 complex links proteins?
Leucine zipper region
Jun dimerisation
can dimerise with itself or with fos
True or False: Fos alone does not form dimers nor bind DNA.
True
Which are more effective: jun/fos heterodimers or jun homodimers?
jun/fos heterodimers
The classical AP-1 complex comprises __ and __
c-jun and c-fos
Jun and fos transcriptional activators act in response to which two pathways?
PKC and Ras
MAPK phosphorylating c-jun increases the ability of c-jun to…
interact with c-fos
How can AP-1 activity be regulated?
by dimer composition, transcription, PTM, interactions with other proteins
True or False: AP-1 has both oncogenic and anti-oncogenic effects.
True
__ is upregulated by AP-1, increasing cell growth and proliferation
EGFR
Functions of myc
- regulate gene transcription
- cell cycle progression
- cooperate with Ras mutations
- involved in chromosomal translocation in some cancers
Myc proteins are localised in the __
nucleus
Myc transcription factor functions as a __
complex/heterodimer
Which signalling pathway leads to the upregulation of c-myc?
Oestrogen
Myc shows homology to…
DNA binding regions of GCN4, fos & jun
Myc associates with the __ protein
max
How does the myc/max complex regulate transcription?
by binding to CACGTG sequences
Myc/max interaction is regulated by __
phosphorylation
Important event in development of Burkitt’s lymphoma in subtropical Africa
myc translocating into the immunoglobulin locus