L5 Gene Regulation

Question 1

different genes possess what?

Answer 1

similar cis-regulatory sequences

Question 2

what are HIF1 alpha and beta?

Answer 2

TFs (heterodimers) that bind to DNA sequences and regulate many genes - when hypoxia is present..

Question 3

when oxygen is high what happens to HIF1alpha and beta?

Answer 3

its proline residues are hydroxylated – ubiquitin to be removed - dont need it! - degraded by prowl hydroxylase domain (PHD) and factor inhibiting HIF1 (FIH) hydroxylases

Question 4

what inhibits PHD and FIH ?

Answer 4

low oxygen - hypoxia —

Question 5

what happens during hypoxia with HIF1 alpha and beta

Answer 5

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)

Question 6

what do hypoxia response elements allow for?

Answer 6

coordinated gene expression in response to anoxia

Question 7

the HIF1 alpha and beta complex must bind to many different…

Answer 7

gene sequences and regulate them in a coordinated fashion - because of the many hot spots

Question 8

what type of TF is glucocorticoid receptor>

Answer 8

zinc-finger TF

Question 9

what does the glucocorticoid receptor do?

Answer 9

up-reg the expression of anti-inflammatory proteins in nucleus

Question 10

what are hormone reponse elements?

Answer 10

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

Question 11

describe the myc oncogene?

Answer 11

promotes expression of a large number of genes involve in cell proliferation

overexpressed in many cancers

Question 12

what are the downstream regulatorys?

Answer 12

ferritin
transferritin
iron responsive element

Question 13

where is glucocorticoid receptors in the absense of glucocorticoid?

Answer 13

cytosplasm - inactive multi-protein complex

Question 14

what is the myc/max system?

Answer 14

a regulatory mech. for switching between gene activation and repression

Question 15

when does gene activation occur?

Answer 15

when both myc and max are made in cell

Question 16

max perfers ___ as a partner?

Answer 16

myc

Question 17

max and myx are always ____

Answer 17

heterodimers!

Question 18

when does gene repression result

Answer 18

only when the max polypeptide is made in the cell - no myc

Question 19

when there is no myc available, what is it?

Answer 19

homodimer - inhibit transcription of genes

Question 20

the myc polypeptide has a transactivation domain which __.

Answer 20

cannot form homodimers or bind DNA

Question 21

max polypeptide can form homodimers and bind DNA which….

Answer 21

has no transactivation domain

Question 22

only the myc-max heterodimer can bind DNA and ___

Answer 22

transactivate

Question 23

overexpression of ___ occurs in many tumors?

Answer 23

MYC - disrupts the equilibrium between activation and repression of genes

Question 24

MAX mutation are a cause of?

Answer 24

hereditary pheochromocytoma

Question 25

what is a target in the treatment of metastatic pheochromocytoma?

Answer 25

MYC

Question 26

what is ferritin?

Answer 26

iron storage protein

Question 27

with low iron what happens with ferritin

Answer 27

ferritin mRNA translation is blocking allowing free iron

Question 28

with high iron what happens with ferritin

Answer 28

ferritin protein is made and excess iron is stored

Question 29

what is transferrin?

Answer 29

iron transport protein

Question 30

in low iron what happens to transferrin?

Answer 30

transferrin mRNA is stabilized to allow translation of more transferrin

Question 31

in high iron, what happens to transferrin?

Answer 31

transferrin mRNA is degraded to reduce protein levels

Question 32

what is the iron-responsive element (IRE)?

Answer 32

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

Question 33

what are iron regulatory proteins (IRPS)?

Answer 33

recognize IREs by trans-acting proteins that control mRNA translation rate and stability

Question 34

there is competition between iron regulatory proteins and 40S ribosome for___

Answer 34

binding to mRNA

Question 35

binding of what prevents binding of ribosome>

Answer 35

IRP-1 or IRP-2 - no protein is produced and iron is not stored and is free for use in the cell