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

Regulation of Gene Expression: HIF-1 Flashcards

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

A

promotes transcription

23
Q

what common protein in this pathway is an E3 ligase

A

VHL (this is part of E3 ligase)

24
Q

what causes Hif1 bidding to VHL

A

hif1 hydroxylation

25
Q

VDU2

A

dismanetles multi-ub chain from conjugated Hif1

26
Q

RBX1

A

required part of E2/3 ubiquitinase protein-if don’t have won’t send Hif1 to proteasome

27
Q

PDH

A

Adds OH groups

Needs Fe2+ to function

28
Q

Normoxia HIF1 pathway

A

HiF1a always in cell

  • PDH adds OH
  • VHL/E3 ligase-ubiquinates
  • proteasome (Unless said by Vdu
29
Q

Hypoxia HIF1 pathway

A

HIF1a created and then goes in nucleus where HIF1B is for trx

30
Q

HIF1beta

A

in nuclelus-needs HIF1a to start trx

31
Q

SIAH1/2

A

Degrades PDH by ubi it-allows HIF1 to survive

32
Q

VHL/E3 ub?

A

Yes-will also cause trx

33
Q

3 mechanisms induce hypoxia

A

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
Q

Reactive Oxygen species

A

Mito failure

Makes Fe2+ to Fe3+

Inhibits PDH activity-possibly cancer

35
Q

DRAW HIF1 ACTIVATION and IkBa ACTIVATION

A

DRAW

36
Q

NFk precursor

A

Must use proteasome to degrade part that makes it inactive

results in p50 and p65

37
Q

Stress

A

activates Ik kinase complex by sending part of it to proteasome
-phosphorylate substrate that is to be put to proteasome

38
Q

Active IkKinase complex

A

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
Q

NFk transcription factor AKA

A

p50/p65

40
Q

Immune response

A

occurs with hypoxia conditions

41
Q

2 parts of hypoxic response

A

Hif1A response

mir210 shuts down exp of normoxia genes

42
Q

Hif1 response pathway is…regulated

A

highly-many proteins afec the regulatory proteins of HIF1 pathway

43
Q

HiF1 synthesis in normoxia

A

constituitive by always degraded

44
Q

Hypoxia and protein synthesis

A

inhibits protein synthesis with micro RNAs

45
Q

Energy metabolism regulators (require what)

A

promote synthesis of HIF

oxygen

46
Q

mTOR and S6 kinase

A

Promote HIF1 translation

47
Q

Difference between O2 dependent and O2 independent (corrected)

A

has limited O2 nd need to increase blood flow

needs growth to take place

48
Q

mir210

A

microRNA

shuts down expression of normoxic genes

49
Q

what molecules does growth hormone encode

A

both mTOR stuff *turn HIF on

MIR-210/155-transcritional control-inhibits normoxia genes

50
Q

HIF1 transcription results in 3 things

A
  1. inhibit normoxia gene expression (miRNA)
  2. accelerate glycolysis (energy metabolism)
  3. Hif1 transcription (NfKb)

something about immune response

51
Q

Mutations in mTOR

A

possibly malignant growth

52
Q

Hif1a stabilization

VHL stab

VDU stab

in regards to cancer

A

increased hypoxia response

reduced HiF1a elvels

higher Hif1a levels

also use proteasome inhibitors ? maybe break up the early factors in pathway

53
Q

Normal acclimatization response

A

fatigue, shortness of breath, increased bp, increased urination, weight loss, poor seep, etc.

54
Q

altitude sickness

how to treat

A

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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