L5 Gene Regulation Flashcards
different genes possess what?
similar cis-regulatory sequences
what are HIF1 alpha and beta?
TFs (heterodimers) that bind to DNA sequences and regulate many genes - when hypoxia is present..
when oxygen is high what happens to HIF1alpha and beta?
its proline residues are hydroxylated – ubiquitin to be removed - dont need it! - degraded by prowl hydroxylase domain (PHD) and factor inhibiting HIF1 (FIH) hydroxylases
what inhibits PHD and FIH ?
low oxygen - hypoxia —
what happens during hypoxia with HIF1 alpha and beta
HIF1 alpha moves into to nucleus of cell where it heterodimerizes with HIB1 beta – they bind to DNA of target genes carrying a hypoxia-reponse element (HRE)
what do hypoxia response elements allow for?
coordinated gene expression in response to anoxia
the HIF1 alpha and beta complex must bind to many different…
gene sequences and regulate them in a coordinated fashion - because of the many hot spots
what type of TF is glucocorticoid receptor>
zinc-finger TF
what does the glucocorticoid receptor do?
up-reg the expression of anti-inflammatory proteins in nucleus
what are hormone reponse elements?
activated GR complex up-reg expression of anti-inflammatory proteins in nucleus
and repress expression of pro-inflammarory proteins in cytosol
inactive multiprotein complex maintained in cytoplasm without glucocorticoid
describe the myc oncogene?
promotes expression of a large number of genes involve in cell proliferation
overexpressed in many cancers
what are the downstream regulatorys?
ferritin
transferritin
iron responsive element
where is glucocorticoid receptors in the absense of glucocorticoid?
cytosplasm - inactive multi-protein complex
what is the myc/max system?
a regulatory mech. for switching between gene activation and repression
when does gene activation occur?
when both myc and max are made in cell
max perfers ___ as a partner?
myc
max and myx are always ____
heterodimers!
when does gene repression result
only when the max polypeptide is made in the cell - no myc
when there is no myc available, what is it?
homodimer - inhibit transcription of genes
the myc polypeptide has a transactivation domain which __.
cannot form homodimers or bind DNA
max polypeptide can form homodimers and bind DNA which….
has no transactivation domain
only the myc-max heterodimer can bind DNA and ___
transactivate
overexpression of ___ occurs in many tumors?
MYC - disrupts the equilibrium between activation and repression of genes
MAX mutation are a cause of?
hereditary pheochromocytoma
what is a target in the treatment of metastatic pheochromocytoma?
MYC
what is ferritin?
iron storage protein
with low iron what happens with ferritin
ferritin mRNA translation is blocking allowing free iron
with high iron what happens with ferritin
ferritin protein is made and excess iron is stored
what is transferrin?
iron transport protein
in low iron what happens to transferrin?
transferrin mRNA is stabilized to allow translation of more transferrin
in high iron, what happens to transferrin?
transferrin mRNA is degraded to reduce protein levels
what is the iron-responsive element (IRE)?
particular hairpin structure located in the 5’ untranslated region or in the 3’ untranslated region of various mRNAs coding for proteins involved in cellular iron metabolism
what are iron regulatory proteins (IRPS)?
recognize IREs by trans-acting proteins that control mRNA translation rate and stability
there is competition between iron regulatory proteins and 40S ribosome for___
binding to mRNA
binding of what prevents binding of ribosome>
IRP-1 or IRP-2 - no protein is produced and iron is not stored and is free for use in the cell
