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BMS 2 > Regulation of Gene Expression: HIF-1 > Flashcards

Regulation of Gene Expression: HIF-1 Flashcards

(54 cards)

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1
Q

hypoxia

A

decreased oxygen to tissues

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2
Q

2 tfs for hpoxia

A

hil1alpha and hil2 alpha

-cleavage

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3
Q

hif1

A

when active promotes increased blood flow, creation of blood, glycolysis, etc. through activation of large number of genes

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4
Q

what promotes degradation of hif1

A

prolyl hydroxlases and lysyl acetylases

-endables recognition by VHL (part of e3/ubi system)

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5
Q

cys-nitrosylation

A

promotes transcription of genes promoted by HIF1

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6
Q

VDU

A

deubiquiniates Hif1

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7
Q

PDH and VHL

A

targets HIF1 for proteasome

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8
Q

O2 dependent vs independent actication

A

dependent-occurs at transcriptional level (changes in metabolism)

independent-changes in protein synthesis

  • trasnlation leel
  • growth factors stimulate mTOR/Sbkinase
  • mir210 inhibits transcription of mormoxic genes
  • occurs under growth conditions
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9
Q

NfKb

A

p50/p56

reduce transcription of genes involves in inflammantory response
-inhibited by Ik-beta

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10
Q

Ik-beta kinase

A

kinase that phosphorylates IkB to make IkB degraded so NfKb can exhibit fucntion

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11
Q

Ik-beta

A

inhibits NfKb-meads ik-beta kinase to get rid of

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12
Q

what is point of being hypoxic

A

provides stimulus for embryogenesis/wound healing/maintains pluripotency of stem cells

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13
Q

ischemia

A

inadequate blood supply to part of body

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14
Q

tumors effects on oxygen conditions

A

make tissue hypoxic

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15
Q

how does high altitude lead to hypoxia

A

air pressure lessens as altitude increases

air holds less molecules and indivudal gas pressure is less

low number of oxygen per area/lower oxygen pressure

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16
Q

barometric pressure vs altitude

A

inverse relationship

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17
Q

symptoms of increased elevation

A

in order of increasing elevation

altered night vision, dizziness, learning/memory impaired, loss of consciousness, hallucinations,, etc.

-also depends how fast you change!

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18
Q

Acclimitization

A

adjustment to higher altitude

  • depends on how high/how fast
  • mediated by Hifi
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19
Q

what promotes hi1 protein synthesis

A

mtor/s6-kinase

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20
Q

what two enzymes control degredation (but both do not degrade)

A

VHL and VDU

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21
Q

what post translational mods promote degradation of Hif1

A

proloyl hydroxylation and lysyl acetylation

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22
Q

cystine nitrosylation

Study These Flashcards
A

promotes transcription

23
Q

what common protein in this pathway is an E3 ligase

Study These Flashcards
A

VHL (this is part of E3 ligase)

24
Q

what causes Hif1 bidding to VHL

Study These Flashcards
A

hif1 hydroxylation

25
VDU2
dismanetles multi-ub chain from conjugated Hif1
26
RBX1
required part of E2/3 ubiquitinase protein-if don't have won't send Hif1 to proteasome
27
PDH
Adds OH groups | Needs Fe2+ to function
28
Normoxia HIF1 pathway
HiF1a always in cell - PDH adds OH - VHL/E3 ligase-ubiquinates - proteasome (Unless said by Vdu
29
Hypoxia HIF1 pathway
HIF1a created and then goes in nucleus where HIF1B is for trx
30
HIF1beta
in nuclelus-needs HIF1a to start trx
31
SIAH1/2
Degrades PDH by ubi it-allows HIF1 to survive
32
VHL/E3 ub?
Yes-will also cause trx
33
3 mechanisms induce hypoxia
target PDH for degredation with Ub (SIAH) - no hydroxyl group added to HIF1 - not recognized for degradation by VHL Target VHL for degradation -no ubi to HIF1 VDU-removes ub chain from HIF 1
34
Reactive Oxygen species
Mito failure Makes Fe2+ to Fe3+ Inhibits PDH activity-possibly cancer
35
DRAW HIF1 ACTIVATION and IkBa ACTIVATION
DRAW
36
NFk precursor
Must use proteasome to degrade part that makes it inactive results in p50 and p65
37
Stress
activates Ik kinase complex by sending part of it to proteasome -phosphorylate substrate that is to be put to proteasome
38
Active IkKinase complex
removes IkBa and send s it to the proteasome so p50/p65 can go be Tfs in nuc removes it by phosphorylation (resulting in multi ub) -probably true for all removal of a subunit
39
NFk transcription factor AKA
p50/p65
40
Immune response
occurs with hypoxia conditions
41
2 parts of hypoxic response
Hif1A response mir210 shuts down exp of normoxia genes
42
Hif1 response pathway is...regulated
highly-many proteins afec the regulatory proteins of HIF1 pathway
43
HiF1 synthesis in normoxia
constituitive by always degraded
44
Hypoxia and protein synthesis
inhibits protein synthesis with micro RNAs
45
Energy metabolism regulators (require what)
promote synthesis of HIF oxygen
46
mTOR and S6 kinase
Promote HIF1 translation
47
Difference between O2 dependent and O2 independent (corrected)
has limited O2 nd need to increase blood flow needs growth to take place
48
mir210
microRNA shuts down expression of normoxic genes
49
what molecules does growth hormone encode
both mTOR stuff *turn HIF on MIR-210/155-transcritional control-inhibits normoxia genes
50
HIF1 transcription results in 3 things
1. inhibit normoxia gene expression (miRNA) 2. accelerate glycolysis (energy metabolism) 3. Hif1 transcription (NfKb) something about immune response
51
Mutations in mTOR
possibly malignant growth
52
Hif1a stabilization VHL stab VDU stab in regards to cancer
increased hypoxia response reduced HiF1a elvels higher Hif1a levels also use proteasome inhibitors ? maybe break up the early factors in pathway
53
Normal acclimatization response
fatigue, shortness of breath, increased bp, increased urination, weight loss, poor seep, etc.
54
altitude sickness how to treat
failure to acclimatize/maladaption - mountain sickness - cerebral/pulmonary edema (swelling) give o2, bring back to low altitude, go slow up mountain, drugs

BMS 2 (41 decks)

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