Cell stress signaling MCQs With Answer

Cell stress signaling MCQs With Answer

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Cell Stress Signaling MCQs With Answer

This quiz set focuses on cell stress signaling pathways relevant to pharmaceutical biotechnology and M.Pharm students. It covers endoplasmic reticulum (ER) stress, unfolded protein response (UPR) sensors (PERK, IRE1α, ATF6), integrated stress response (ISR), oxidative stress signaling (Nrf2-Keap1), MAPK cascades (JNK, p38), heat shock response, autophagy, proteasomal degradation and apoptosis triggered by proteostasis imbalance. Questions emphasize molecular mechanisms, key regulators, drug targets and translational control under stress. Designed to deepen conceptual understanding and support exam preparation, these 20 MCQs include concise answers to help you evaluate readiness for advanced coursework and research applications in therapeutic modulation of stress pathways.

Q1. Which three transmembrane proteins function as the primary sensors of unfolded protein accumulation in the endoplasmic reticulum?

  • PERK, IRE1α and ATF6
  • mTOR, AMPK and PDK1
  • JNK, p38 and ERK
  • HSP70, HSP90 and CHIP

Correct Answer: PERK, IRE1α and ATF6

Q2. Phosphorylation of eIF2α during ER stress primarily leads to which of the following cellular outcomes?

  • Global translation attenuation with selective translation of ATF4
  • Activation of mTORC1 and increased protein synthesis
  • Direct activation of proteasome subunits to increase degradation
  • Immediate ubiquitination of misfolded ER proteins

Correct Answer: Global translation attenuation with selective translation of ATF4

Q3. The endoribonuclease activity of IRE1α mediates which critical processing event during the unfolded protein response?

  • Unconventional splicing of XBP1 mRNA to generate XBP1s
  • Cleavage of ATF6 into a soluble transcription factor
  • Direct cleavage of eIF2α to stop translation
  • Processing of pro-caspase-3 into active caspase-3

Correct Answer: Unconventional splicing of XBP1 mRNA to generate XBP1s

Q4. Activation of ATF6 during ER stress requires which sequence of events?

  • Translocation to the Golgi and proteolytic cleavage by S1P/S2P
  • Phosphorylation by PERK and subsequent dimerization
  • Ubiquitination and proteasomal processing to a transcription factor
  • Direct binding to misfolded proteins and nuclear import

Correct Answer: Translocation to the Golgi and proteolytic cleavage by S1P/S2P

Q5. Which transcription factor is strongly induced by prolonged ER stress and promotes pro-apoptotic gene expression such as through downregulation of Bcl-2?

  • CHOP (GADD153)
  • HIF-1α
  • NF-κB
  • CREB

Correct Answer: CHOP (GADD153)

Q6. Under oxidative stress, which regulatory protein releases Nrf2 allowing it to translocate to the nucleus and activate antioxidant response element (ARE) genes?

  • Keap1
  • Parkin
  • Atg7
  • GRP78/BiP

Correct Answer: Keap1

Q7. IRE1α can activate pro-apoptotic JNK signaling through which adaptor protein?

  • TRAF2
  • 14-3-3
  • GRB2
  • p62/SQSTM1

Correct Answer: TRAF2

Q8. Which eIF2α kinase is primarily responsible for sensing ER stress and phosphorylating eIF2α as part of the unfolded protein response?

  • PERK
  • GCN2
  • PKR
  • HRI

Correct Answer: PERK

Q9. How does autophagy typically contribute to the cellular response to proteotoxic stress?

  • By degrading aggregated proteins and damaged organelles to restore proteostasis
  • By increasing global protein synthesis to dilute misfolded proteins
  • By directly cleaving misfolded proteins in the ER lumen
  • By exporting misfolded proteins intact to the extracellular space

Correct Answer: By degrading aggregated proteins and damaged organelles to restore proteostasis

Q10. Which clinical drug acts as a proteasome inhibitor and induces proteotoxic stress in cancer cells?

  • Bortezomib
  • Rapamycin
  • Imatinib
  • Metformin

Correct Answer: Bortezomib

Q11. The heat shock response is transcriptionally regulated by which master transcription factor that senses proteotoxic stress and induces HSP expression?

  • HSF1
  • NFAT
  • STAT3
  • FOXO3a

Correct Answer: HSF1

Q12. Which nutrient-sensing complex, when active, suppresses autophagy and promotes protein synthesis?

  • mTORC1
  • AMPK
  • ULK1
  • IRE1α

Correct Answer: mTORC1

Q13. A reliable biochemical indicator of intracellular oxidative stress is a change in which ratio?

  • Reduced glutathione to oxidized glutathione (GSH/GSSG) ratio
  • ATP/ADP ratio
  • NAD+/NADH ratio
  • cAMP/cGMP ratio

Correct Answer: Reduced glutathione to oxidized glutathione (GSH/GSSG) ratio

Q14. ASK1 (apoptosis signal-regulating kinase 1) is activated by oxidative stress through dissociation from which inhibitory thiol-containing protein?

  • Thioredoxin (Trx)
  • Keap1
  • HSP90
  • Protein disulfide isomerase (PDI)

Correct Answer: Thioredoxin (Trx)

Q15. Which of the following best summarizes the adaptive aims of the unfolded protein response (UPR)?

  • Reduce ER protein load, increase folding capacity and enhance degradation of misfolded proteins
  • Increase global protein synthesis, inhibit chaperone expression and block ERAD
  • Activate mitochondrial biogenesis and inhibit lysosomal function
  • Promote immediate cell cycle progression and DNA replication

Correct Answer: Reduce ER protein load, increase folding capacity and enhance degradation of misfolded proteins

Q16. What does RIDD refer to in the context of IRE1α signaling?

  • Regulated IRE1-dependent decay of specific mRNAs
  • Rapid induction of DNA damage
  • Ribosomal inactivation during ER stress
  • Reversible inhibition of deubiquitinases

Correct Answer: Regulated IRE1-dependent decay of specific mRNAs

Q17. Which caspase is predominantly implicated in ER stress–induced apoptosis in human cells?

  • Caspase-4
  • Caspase-8
  • Caspase-9
  • Caspase-12

Correct Answer: Caspase-4

Q18. The integrated stress response (ISR) links multiple upstream kinases to eIF2α phosphorylation. Which transcription factor is preferentially translated during ISR to regulate adaptive genes?

  • ATF4
  • NF-κB
  • c-Myc
  • p53

Correct Answer: ATF4

Q19. HSP90 inhibitors (e.g., geldanamycin analogs) affect client oncoproteins primarily by which mechanism?

  • Destabilizing client proteins leading to ubiquitination and proteasomal degradation
  • Enhancing chaperone-mediated refolding to rescue misfolded proteins
  • Blocking transcription of chaperone genes at the promoter
  • Increasing lysosomal fusion to degrade mitochondria selectively

Correct Answer: Destabilizing client proteins leading to ubiquitination and proteasomal degradation

Q20. Excessive ER calcium release during stress contributes to mitochondrial dysfunction by promoting which event that triggers apoptosis?

  • Opening of the mitochondrial permeability transition pore (mPTP)
  • Inhibition of complex IV leading to increased ATP production
  • Stabilization of mitochondrial membrane potential preventing cytochrome c release
  • Activation of lysosomal hydrolases that repair mitochondria

Correct Answer: Opening of the mitochondrial permeability transition pore (mPTP)

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