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Related Concept Videos

Physiological Foundation of Stress01:24

Physiological Foundation of Stress

56
Stress triggers a coordinated physiological response involving the sympathetic nervous system (SNS) and the hypothalamic-pituitary-adrenal (HPA) axis. This dual activation ensures that the body is prepared for both immediate and prolonged stress management. The process begins with the perception of a stressor. This initial phase activates the SNS, leading to the rapid release of adrenaline (epinephrine) from the adrenal glands.
Role of the Sympathetic Nervous System
Adrenaline triggers the...
56
Regulation of the Unfolded Protein Response01:31

Regulation of the Unfolded Protein Response

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Inositol-requiring kinase one or IRE1 is the most conserved eukaryotic unfolded protein response (UPR) receptor. It is a type I transmembrane protein kinase receptor with a distinctive site-specific RNase activity. As the binding mechanics of the misfolded proteins with the N-terminal domain of IRE-1 are unclear, three binding models — direct, indirect, and allosteric -- are proposed for receptor activation. Nevertheless, it is known that once a misfolded protein associates with IRE1, it...
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The Unfolded Protein Response01:37

The Unfolded Protein Response

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The ER is the hub of protein synthesis in a cell. It has robust systems to quality control protein folding and also for degradation of terminally misfolded proteins. Under normal conditions, a small proportion of misfolded proteins that cannot be salvaged need to be transported to the cytoplasm by the ER-associated degradation or ERAD pathways. However, if the ERAD cannot handle the misfolded proteins, the cell activates the unfolded protein response or UPR to adjust the protein folding...
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Introduction to Stress and Lifestyle01:27

Introduction to Stress and Lifestyle

106
Stress is a multifaceted response to events perceived as challenging or threatening, highlighting physical, emotional, cognitive, and behavioral reactions. Physically, stress can lead to fatigue, sleep disruptions, and various health issues such as frequent colds, chest pains, and nausea. Emotionally, it can manifest as anxiety, depression, irritability, and anger triggered by both minor and major life events. Cognitively, it may result in difficulty in concentration, memory, and...
106
Psychological Responses to Stress01:20

Psychological Responses to Stress

54
Psychological responses to stress encompass the various cognitive and emotional reactions individuals experience when faced with challenging or threatening situations, such as a job loss. Prolonged exposure to stressors can disturb emotional balance, increasing negative emotions (e.g., anxiety and sadness) and diminishing positive emotions (e.g., joy and satisfaction). These persistent emotional shifts are associated with an increased risk of both physical illness and mental health issues, such...
54
Stress Response System01:21

Stress Response System

90
The stress response system, also known as the fight-or-flight response, is the body's automatic physiological reaction to perceived threats. Hans Selye introduced the concept of General Adaptation Syndrome (GAS) to describe the predictable pattern of changes that occur in response to stress. GAS consists of three sequential stages: alarm, resistance, and exhaustion. This model helps explain how chronic stress can contribute to health problems.
Alarm stage
In the alarm stage, the body's...
90
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  9. Predictive And Prognostic Markers
  11. Integrated Stress Response Plasticity Governs Normal Cell Adaptation To Chronic Stress Via The Pp2a-tfe3-atf4 Pathway.
  1. Home
  3. Research Domains
  5. Biomedical And Clinical Sciences
  7. Oncology And Carcinogenesis
  9. Predictive And Prognostic Markers
  11. Integrated Stress Response Plasticity Governs Normal Cell Adaptation To Chronic Stress Via The Pp2a-tfe3-atf4 Pathway.

Related Experiment Video

Measurements of Physiological Stress Responses in C. Elegans
10:36

Measurements of Physiological Stress Responses in C. Elegans

Published on: May 21, 2020

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Integrated stress response plasticity governs normal cell adaptation to chronic stress via the PP2A-TFE3-ATF4 pathway.

Rita A Avelar1,2, Riya Gupta1,2, Gracie Carvette1,2

  • 1Department of Pathology, The University of Michigan, Ann Arbor, MI 48109, USA.

Research Square
|April 8, 2024

View abstract on PubMed

Summary
This summary is machine-generated.

The integrated stress response (ISR) adapts cells to stress. PP2A activation by modulating ISR plasticity offers a new strategy for selective cancer cell death and improved cancer therapies.

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Area of Science:

  • Cell Biology
  • Molecular Biology
  • Oncology

Background:

  • The integrated stress response (ISR) is crucial for cell fate regulation under stress.
  • Protein phosphatase 2A (PP2A) activity modulation shows therapeutic promise in cancer, but mechanisms are unclear.

Approach:

  • Investigated the role of PP2A in ISR plasticity and its impact on cellular fate.
  • Utilized genetic and chemical modulation of PP2A to induce chronic stress and ISR.
  • Identified the PP2A-TFE3-ATF4 pathway governing ISR during stress, independent of the unfolded protein response.

Key Points:

  • PP2A activation is essential for ISR plasticity, influencing drug response and cell fate.
  • Normal cells adapt to PP2A-mediated stress via ISR, ensuring homeostatic recovery.
  • Cancer cells exhibit irreversible ISR upon PP2A modulation, leading to selective cytotoxicity.

    • Conclusions:

    • ISR plasticity determines differential responses to PP2A modulation.
    • Targeting PP2A-mediated ISR offers a novel vulnerability for selective cancer cell death.
    • This approach could enhance targeted cancer therapeutic efficacy.