Reading a Stress Signal to Its Output | AI Learning Guide

Use the comparison as a decision procedure. Start with the disturbance, not the outcome. A proteasome inhibitor creates misfolded protein, so the chaperone pool is titrated and HSF1 is released; translation stays on because nothing has limited ternary complex. Amino acid starvation creates uncharged tRNA, so GCN2 phosphorylates eIF2alpha; translation drops and ATF4 rises. Same cell, different sensor, different program. Then look at the note. If both stressors occur together, you do not get a blended program. You get both programs running at once, and the translational block now limits how fast the cell can make the chaperones it needs. That tension is worth remembering.

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Sensor identity determines the transcription factor and whether translation is reprogrammed. Ask which disturbance is present, which sensor detects it, and whether eIF2alpha is phosphorylated. Those three answers predict the output program.

Two stressors, two output programs

Proteasome inhibitor

Disturbance: misfolded and ubiquitinated protein
Sensor engaged: chaperone titration
Transcription factor: HSF1
Translation: largely unchanged
Output: chaperones and proteasome subunits

Amino acid starvation

Disturbance: uncharged tRNA
Sensor engaged: GCN2
Transcription factor: ATF4
Translation: globally suppressed, ATF4 favored
Output: amino acid transporters and synthetases

When two stressors are present at once, the outputs superimpose. A translational block can limit synthesis of the very chaperones the folding program needs, which is a trade-off rather than a contradiction.