B2.053 Prework 2 Regulation of Protein Translation Flashcards Preview

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Flashcards in B2.053 Prework 2 Regulation of Protein Translation Deck (20)
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1

what are 2 mechanisms of translational regulation?

1. general factors (eIF) - broad/global
2. microRNA (miRNA) - specific

2

what is the endoplasmic reticulum stress response?

secreted/cell surface proteins are synthesized in ER
stress conditions: proteins fold incorrectly, accumulate in the ER

3

what types of stressers contribute to ER stress?

calcium depletion
reduction of disulfide bonds
expression of mutant proteins
ischemia
UV light exposure

4

what are the 4 kinases that can phosphorylate eIF2a and inhibit translation?

1. PKR - activated by viral dsRNA
2. GCN5 - activated by low amino acids/ glucose (nutritional stress)
3. HRI - activated by low heme only in immature erythrocytes
4. PERK - activated by ER stress/unfolded proteins

5

describe the pathway by which PERK shuts down transcription

PERK kinase activated
PERK phosphorylates eIF2a
phosphor-eIF2a cannot participate in initiation

6

what are the two outcomes of eIF2a phosphorylation?

1. most protein translation stops
2. transcription of specific mRNAs into protein increases

7

what transcription factor is activated with P-eIF2a?

ATF4
upregulates pro recovery mechanisms
Proteases
Chaperones
Anti-oxidants

8

what protein activated by ATF4 leads to apoptosis?

CHOP
over time, builds up to sufficient amount to stimulate apoptosis

9

what is the function of 4E binding proteins?

bind/sequester eIF4E
release eIF4E when phosphorylated

10

how does insulin influence 4E BPs?

insulin stimulates a kinase cascade that phosphorylates 4E-BP and releases eIF4E to increase translation

11

what are micro RNAs?

21/22 nucleotide RNAs
coded for by specific genes
processed from longer RNA transcripts
repress translation and cause mRNA degradation

12

were do miRNAs bind to mRNAs?

3'UTR
UTR=untranslated region

13

what is the structure of miRNAs?

hairpin structure with intramolecular base pairing

14

what protein complex is associated with miRNAs?

RNA-induced silencing complex, RISC

15

what is the difference between the effects of siRNAs and miRNAs?

siRNAs induce mRNA degradation
miRNA decrease translation and induce mRNA degradation

16

discuss the potential therapeutic application of miRNAs

potential therapeutic approach: silence expression of protein required for pathology
dsRNA oligonucleotides delivered as "drug"
called RNAi (RNA interference)

17

what is the function of about 1/2 of antibiotics?

inhibit bacterial translation to kill the bacteria

18

what is important about using translation inhibitor antibiotics?

they inhibit the synthesis of bacterial toxins even before the bacteria itself is killed

19

what is an example of a bacterial translation inhibitor?

aminoglycosides (streptomycin)
bind to 30S subunit of bacterial ribosome

20

what are 3 mechanisms by which aminoglycosides can inhibit translation?

block initiation
block further translation and elicits premature termination
incorporation of incorrect amino acid