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Changes in Signal Transduction Pathways

When a chemical signal binds to receptors on the surface of a cell, it sends out a signal that is relayed through the activation of one molecule after another. This is called a signal transduction pathway, and these pathways involve many proteins and enzymesSo, when any of these components are changed, cellular processes can become dysregulated and cause cancer and other diseases.

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Changes in Signal Transduction Pathways

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When a chemical signal binds to receptors on the surface of a cell, it sends out a signal that is relayed through the activation of one molecule after another. This is called a signal transduction pathway, and these pathways involve many proteins and enzymes. So, when any of these components are changed, cellular processes can become dysregulated and cause cancer and other diseases.

Here, we will review what cell signaling and signal transduction pathways before delving into what causes changes in signal transduction pathways and what effects these changes have on various cellular processes. We will also look into specific examples of these changes!

Recap: Cell Signaling And Signal Transduction Pathways

Cells respond to signals from its environment through cell signaling, a process in which a signaling molecule called ligand binds to a receptor protein in or on the surface of the target cell, initiating a specific cellular response.

The process of cell signaling takes place in three basic steps:

  1. Signal reception: the ligand binds to the receptor protein in or on the surface of the target cell.

  2. Signal transduction: the binding of the ligand to the receptor sends a signal that is relayed by receptors or second messengers in a signaling pathway. This step takes place when a ligand binds to a cell-surface receptor. On the other hand, if the ligand binds to an intracellular receptor, the receptor diffuses across the plasma membrane so they do not need to transmit the signal to other receptors or messengers via signal transduction.

  3. Cellular response: the signal reaches its target protein and ultimately initiates a specific cellular process.

Cell signaling must be regulated so that the products of the reactions that are triggered by signaling molecules are produced at the proper time and place. Cell signaling is typically regulated by monitoring and controlling protein levels, localizing protein activities, and modifying the signaling molecule after translation.


Changes In Signal Transduction Pathways Overview

Signal transduction pathway (or signal cascade) refers to the branched molecular network that successively activates (or deactivates) signaling molecules to perform a certain biological function.

When there are changes or disruptions in signal transduction pathways, cellular response may be affected, or in worse cases, cause life-threatening diseases like cancer.

Causes Of Changes In Signal Transduction Pathways

So, what causes changes in signal transduction pathways? In this section, we will discuss three major causes: environmental conditions, mutations, and the presence of inhibitor or activator molecules.

Environmental Conditions

When environmental conditions such as temperature or pH are altered beyond a cell’s livable range, proteins and enzymes in signal transduction pathways can be denatured and lose their ability to function properly.

Denaturation refers to the modification of the molecular structure of a protein (Fig. 1). This involves breaking down weak bonds within a protein molecule that give the protein its highly ordered structure. For this reason, cells that are exposed to conditions outside of their livable range can die.

Mutations

Proteins and enzymes that take part of signal transduction are produced through protein synthesis. Protein synthesis depends on the nucleotide sequence within DNA, so any mutation in DNA will eventually have an impact on the protein that the mutated genes code for.

Because there are so many proteins in a single signal transduction pathway, there is a high risk of pathway disruption. However, not all proteins disrupt the system in the same way.

For example, if the gene that codes for the receptor protein is altered, the whole signal transduction pathway would be disrupted. In contrast, if an enzyme at the end of the signal cascade is altered, the impact on the pathway as a whole may be smaller since this enzyme is just one of hundreds or thousands that are responding to the original signal.

Inhibitors and Activator Molecules

A signal transduction pathway can be altered by a variety of inhibitors and activators, including substances like pesticides and some medications.

There are many different kinds of inhibitors that have the power to alter an enzyme's role in a signal transduction pathway, including:

  • Competitive inhibitors physically block the active site, preventing the substrate from entering.

  • Noncompetitive inhibitors bind to a different site on the enzyme but also hinder reaction catalysis.

  • Uncompetitive inhibitors bind to the enzyme-substrate complex, thereby preventing catalysis.

On the other hand, activators are molecules that reversibly or irreversibly bind to receptor proteins. Activators have the ability to activate pathways that would not have been activated otherwise. Many pesticides, for example, are strong activators of signal transduction pathways in neurons, resulting in hyperactivity in insect brains and, eventually, death.

Example Of How Changes In Signal Transduction Pathways Alter Cellular Response

In this section, we will discuss how changes in signal transduction pathways cause changes in cellular response. We will tackle two specific examples: changes in the insulin signaling pathway as well as cancer-causing dysregulation of signal transduction pathways.

Changes In Insulin Signaling Pathways

The hormone insulin is produced by the beta-cells in the pancreas. When pancreatic cells detect high levels of glucose in the bloodstream, insulin is released. Insulin molecules travel through the bloodstream until each molecule reaches a receptor tyrosine kinase protein on its target cells.

The binding of insulin with the receptor tyrosine kinase causes the dimerization of RTK proteins, which then causes the phosphorylation of their intracellular domains. Then, a phosphorylation cascade is initiated, activating a series of reactions all over the cell, including the binding of a vesicle containing glucose importers with the cell membrane, which then imports glucose from the bloodstream.

What happens when there are changes in this signaling pathway? Let’s say there is a mutation in the gene involved in the production of insulin, changing its shape or chemistry and thereby altering its ability to bind to the receptor. If this happens, the entire signal transduction pathway can be disrupted. This genetic condition causes neonatal diabetes.

Likewise, the genes that code for insulin receptors can be inherited with potentially dangerous mutations, resulting in Donohue syndrome which leads to leprechaunism, which manifests in the affected individual as small stature, bulging eyes, upturned nostrils, and thick lips. These mutations are extremely harmful because they occur at the start of the signal transduction pathway, resulting in full breakdown of the entire route.

Dimerization refers to the production of a dimer from two identical monomer units.

Phosphorylation is the addition of a phosphate group, while phosphorylation cascade is when phosphorylation takes place one after another, causing a series of reactions.

Cancer-causing Types Of Changes In Signal Transduction Pathways

Cancer causes increased cell proliferation–including resistance to apoptosis and other forms of cell death–genetic instability, metabolic changes, and a host of other definitive features, most of which are due to the dysregulation of signal transduction pathways.

The dysregulation of signal transduction pathways can be caused by oncogenic mutations which cause genes to be over expressed or produce proteins with dysregulated activities (Fig. 2).

Proteins affected by these mutations include growth factor receptor tyrosine kinases, lipid kinases, and nuclear receptors which are commonly activated in many physiological responses. Components of developmental signaling pathways such as Notch receptors, as well as downstream nuclear targets such as transcription factors can also be affected.

Another cause of dysregulation is the deletion or mutation of negative regulators which typically function as tumor suppressors, inactivating them. For example, one of the most common mutated genes is a tumor suppressor called p53 which regulates cell proliferation and stress signals that lead to apoptosis and damage responses. When p53 is lost due to deletion or mutation, it can contribute to cancer by reducing cell death and dysregulating the cell cycle.

Apoptosis, or programmed cell death is a mechanism that allows cells to die in a controlled way to prevent potentially harmful molecules from leaving the cell and causing damage to other cells.

Changes in Signal Transduction Pathways - Key takeaways

  • Signal transduction pathway (or signal cascade): the branched molecular network that successively activates (or deactivates) signaling molecules to perform a certain biological function.
  • When there are changes or disruptions in signal transduction pathways, cellular response may be affected, or in worse cases, cause life-threatening diseases like cancer.
  • When environmental conditions such as temperature or pH are altered beyond a cell’s livable range, proteins and enzymes in signal transduction pathways can be denatured and lose their ability to function properly.
  • Any mutation in DNA will eventually have an impact on the protein that the mutated genes code for. However, not all proteins disrupt the system in the same way.
  • A signal transduction pathway can also be altered by a variety of inhibitors and activators.

References

  1. Sever R, Brugge JS. Signal transduction in cancer. Cold Spring Harb Perspect Med. 2015 Apr 1;5(4):a006098. doi: 10.1101/cshperspect.a006098. PMID: 25833940; PMCID: PMC4382731.
  2. “Origins of Cell Compartmentalization | AP Biology | Biology Dictionary.” Biology Dictionary, biologydictionary.net, 18 Dec. 2016, https://biologydictionary.net/ap-biology/4-4-changes-in-signal-transduction-pathways/.
  3. Denaturation | Definition, Examples, & Facts.” Encyclopedia Britannica, www.britannica.com, https://www.britannica.com/science/denaturation. Accessed 2 Aug. 2022.
  4. Reece, Jane B., et al. Campbell Biology. Eleventh ed., Pearson Higher Education, 2016.
  5. Zedalis, Julianne, et al. Advanced Placement Biology for AP Courses Textbook. Texas Education Agency.
  6. Lee MJ, Yaffe MB. Protein Regulation in Signal Transduction. Cold Spring Harb Perspect Biol. 2016 Jun 1;8(6):a005918. doi: 10.1101/cshperspect.a005918. PMID: 27252361; PMCID: PMC4888820.

Frequently Asked Questions about Changes in Signal Transduction Pathways

Changes in signal transduction pathways alter cellular response by modifying or dysregulating the functions of various component proteins or enzymes.

Factors that could interfere with proper functioning of the signal transduction pathway include environmental conditions causing proteins to be denatured, mutations, and presence of inhibitors or activator molecules.

Protein modification in a signal transduction pathway can alter cellular functions or responses. 

Cell signaling must be regulated so that the products of the reactions that are triggered by signaling molecules are produced at the proper time and place. Cell signaling is typically regulated by monitoring and controlling protein levels, localizing protein activities, and modifying the signaling molecule after translation.

Abnormal signal transduction is when the components of a signal transduction pathway are altered, causing changes to cellular response.

Final Changes in Signal Transduction Pathways Quiz

Changes in Signal Transduction Pathways Quiz - Teste dein Wissen

Question

This process can be described as a self-destruct mechanism that allows cells to die in a controlled way, preventing potentially harmful molecules from escaping the cell.

Show answer

Answer

Apoptosis

Show question

Question

During this process, cells that die swell, burst, and empty their contents onto their neighbors.

Show answer

Answer

Necrosis

Show question

Question

During this process, a type of white blood cell envelopes and destroys a foreign substance or removes dead cells. This process plays a role in preventing the contents of dying cells from being released.

Show answer

Answer

Phagocytosis

Show question

Question

What enzyme initiates apoptosis by cleaving specific proteins in the nucleus and cytoplasm?

Show answer

Answer

Caspase

Show question

Question

Explain the process of caspase cascade.

Show answer

Answer

Caspases are enzymes that cleave specific proteins in the nucleus and cytoplasm. Caspases can be found in all cells as inactive precursors that are activated via cleavage by other caspases. Active caspases cleave and activate other procaspases, resulting in what is called a caspase cascade.

Show question

Question

Explain how the mitochondrial process works.

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Answer

For cell damage to trigger apoptosis, a gene called p53 is required to start the transcription of genes that stimulate the release of cytochrome c--an electron carrier protein--from mitochondria. Once cytochrome c is forced out of mitochondria and into the cytosol, it interacts and activates the adaptor protein Apaf-1. Most forms of apoptosis utilize this mitochondrial pathway of procaspase activation to start, speed up, or intensify the caspase cascade.


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Question

Immune cells called T-cells are used by the immune system to target and destroy foreign macromolecules and particles by binding to them. How does the development of T-cells trigger apoptosis?

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Answer

T-cells normally don't target self-proteins (those produced by their own bodies). If they do, it can result in autoimmune disease. For this reason, immature T-cells are screened to see whether they attach to so-called self-proteins so that they can develop the ability to distinguish between self and non-self. Should the T-cell receptor attach to self-proteins, the cell initiates apoptosis to kill any potentially harmful cells.

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Question

How is the activation of the apoptosis pathway regulated?

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Answer

The apoptosis pathway is regulated by intracellular and extracellular signals that promote or suppress activation.

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Question

Explain how apoptosis plays a role in the formation of mouse paws.

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Answer

During the embryonic development of mice, apoptosis occurs in the cells in between individual fingers. As such, cell death sculpts their paws by causing the individual fingers to break apart from what is initially a spade-like structure. 

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Question

How is apoptosis related to cancer?

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Answer

When apoptosis does not function properly, cells with potentially dangerous mutations may not be eliminated. Instead, such cells can grow uncontrollably, leading to the formation of a tumor. This happens because some sensors in cancer cells may fail to recognize signals that trigger apoptosis. 


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Question

What is cellular blebbing?

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Answer

Cellular blebbing is a feature of a cell undergoing apoptosis in which the plasma membrane forms bulges.

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Question

What gene is required to trigger apoptosis in the mitochondrial pathway?

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Answer

p53

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Question

Explain the role of the IAP family in regulating apoptosis.

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Answer

The inhibitor of apoptosis (IAP) family prevents cell death in two ways: first, by binding to certain procaspases, they stop them from activating, and second, by binding to caspases, they stop them from being active. The efficacy of the death activation mechanism is considerably increased when mitochondria release cytochrome c to activate Apaf-1 together with a protein that inhibits IAPs.

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Question

Why is it important to regulate apoptosis?

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Answer

A cell cannot turn back once it has reached a key stage along the road to its demise because the caspase cascade is not only destructive but also self-amplifying. As such, it is important that mechanisms that regulate apoptosis are in place. 

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Question

When do cells undergo apoptosis?

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Answer

When cells are damaged.

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Question

What is denaturation?

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Answer

Denaturation refers to the modification of the molecular structure of a protein. This involves breaking down weak bonds within a protein molecule that give the protein its highly ordered structure. 

Show question

Question

How does denaturation affect signal transduction?

Show answer

Answer

By modifying their structure, denaturation causes proteins and enzymes to lose their ability to function properly.

Show question

Question

What are the typical causes of denaturation?

Show answer

Answer

Extreme temperatures and pH

Show question

Question

How do mutations change signal transduction pathways?

Show answer

Answer

Proteins and enzymes that take part of signal transduction are produced through protein synthesis. Protein synthesis depends on the nucleotide sequence within DNA, so any mutation in DNA will eventually have an impact on the protein that the mutated genes code for. 

Show question

Question

Do mutations affect signal transduction pathways equally? Why or why not?

Show answer

Answer

Mutations affect signal transduction pathways differently. 

For example, if the gene that codes for the receptor protein is altered, the whole signal transduction pathway would be disrupted. In contrast, if an enzyme at the end of the signal cascade is altered, the impact on the pathway as a whole may be smaller since this enzyme is just one of hundreds or thousands that are responding to the original signal. 

Show question

Question

____ physically block the active site, preventing the substrate from entering.

Show answer

Answer

Competitive inhibitors 

Show question

Question

What are activator molecules?

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Answer

Activator molecules reversibly or irreversibly bind to receptor proteins. 

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Question

How do activator molecules affect signal transduction pathways?

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Answer

Activators have the ability to activate pathways that would not have been activated otherwise. 

Show question

Question

What happens when the genes that encode for the production of a ligand undergo a mutation?

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Answer

The ligand might have an altered shape or chemistry, thereby altering its ability to bind to the receptor. 

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Question

When does mutation not have a great impact on a signal transduction pathway?

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Answer

The impact of mutation of a gene that encodes proteins involved in cell signaling is not as great when the proteins involved are further downstream or closer to the end.

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Question

What are oncogenic mutations?


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Answer

Oncogenic mutations cause genes to be overexpressed or produce proteins with dysregulated activities

Show question

Question

How can changes in signal transduction pathways cause cancer?

Show answer

Answer

Cancer causes increased cell proliferation–including resistance to apoptosis and other forms of cell death–genetic instabilitymetabolic changes, and a host of other definitive features, most of which are due to the dysregulation of signal transduction pathways.

Show question

Question

How does a mutation in p53 gene cause cancer?

Show answer

Answer

p53 is a tumor suppressor gene which regulates cell proliferation and stress signals that lead to apoptosis and damage responses. When p53 is lost due to deletion or mutation, it can contribute to cancer by reducing cell death and dysregulating the cell cycle. 

Show question

Question

How is a signal transduction pathway regulated?

Show answer

Answer

Cell signaling must be regulated so that the products of the reactions that are triggered by signaling molecules are produced at the proper time and place. Cell signaling is typically regulated by monitoring and controlling protein levels, localizing protein activities, and modifying the signaling molecule after translation. 

Show question

Question

___ bind to the enzyme-substrate complex, thereby preventing catalysis.

Show answer

Answer

Uncompetitive inhibitors

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Question

What is the main difference between hypoxia and hypoxemia?

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Answer

Hypoxia refers to a deficiency of oxygen in body tissues, while hypoxemia refers to low oxygen levels in the blood.

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What are some common physical symptoms of hypoxia?

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Answer

Shortness of breath, rapid or shallow breathing, increased heart rate, weakness or fatigue, swelling in extremities, cyanosis, chest pain, and dizziness or fainting.

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Which factors can contribute to hypoxemia?

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Answer

Impaired lung function, high altitudes, anemia, and exposure to harmful substances like carbon monoxide.

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What are some major causes of cerebral hypoxia?

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Stroke, cardiac arrest, choking or airway obstruction, drowning, carbon monoxide poisoning, and certain medical conditions.

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What are possible long-term consequences of cerebral hypoxia?

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Answer

Cognitive deficits, physical disabilities, emotional or behavioural issues, and epilepsy or seizure disorders.

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Question

What preventive measures can be taken to minimize the risk of cerebral hypoxia?

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Answer

Managing underlying medical conditions, using proper safety equipment, acclimatising to high altitudes, avoiding hazardous environments, and practicing healthy lifestyle habits.

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Question

What are the three levels of hypoxia based on where oxygen deficiency occurs?

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Answer

Systemic hypoxia, tissue hypoxia, and cellular hypoxia

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Question

What is a significant environmental factor contributing to hypoxia?

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Answer

High altitude, due to reduced atmospheric pressure leading to lower oxygen levels in the air

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Question

Name one physiological or pathological cause of hypoxia.

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Answer

Respiratory disorders, such as asthma, COPD, or pneumonia, impairing lung function and causing inadequate oxygenation of the blood

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Question

What is the cornerstone of hypoxia treatment?

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Answer

Providing supplemental oxygen to increase oxygen delivery to tissues.

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Question

What are some immediate interventions for hypoxia?

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Answer

Oxygen therapy, airway management, mechanical ventilation, administration of bronchodilators, and use of vasopressors.

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Question

What are some long-term management and prevention strategies for hypoxia?

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Answer

Addressing underlying conditions, prescribing medications, implementing lifestyle changes, and using preventative measures.

Show question

Test your knowledge with multiple choice flashcards

This process can be described as a self-destruct mechanism that allows cells to die in a controlled way, preventing potentially harmful molecules from escaping the cell.

During this process, cells that die swell, burst, and empty their contents onto their neighbors.

During this process, a type of white blood cell envelopes and destroys a foreign substance or removes dead cells. This process plays a role in preventing the contents of dying cells from being released.

Next

Flashcards in Changes in Signal Transduction Pathways42

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This process can be described as a self-destruct mechanism that allows cells to die in a controlled way, preventing potentially harmful molecules from escaping the cell.

Apoptosis

During this process, cells that die swell, burst, and empty their contents onto their neighbors.

Necrosis

During this process, a type of white blood cell envelopes and destroys a foreign substance or removes dead cells. This process plays a role in preventing the contents of dying cells from being released.

Phagocytosis

What enzyme initiates apoptosis by cleaving specific proteins in the nucleus and cytoplasm?

Caspase

Explain the process of caspase cascade.

Caspases are enzymes that cleave specific proteins in the nucleus and cytoplasm. Caspases can be found in all cells as inactive precursors that are activated via cleavage by other caspases. Active caspases cleave and activate other procaspases, resulting in what is called a caspase cascade.

Explain how the mitochondrial process works.

For cell damage to trigger apoptosis, a gene called p53 is required to start the transcription of genes that stimulate the release of cytochrome c--an electron carrier protein--from mitochondria. Once cytochrome c is forced out of mitochondria and into the cytosol, it interacts and activates the adaptor protein Apaf-1. Most forms of apoptosis utilize this mitochondrial pathway of procaspase activation to start, speed up, or intensify the caspase cascade.


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