Name: caspases in apoptosis and immunity
Uploaded: 2023-04-30T10:28:04.000Z
Duration: 1 min 24 s
Channel: JoVE

Cysteine-dependent aspartate-specific proteases, shortened to caspases, are proteases that break down specific cellular proteins and induce apoptosis.
The cysteine residue located in the caspase active site cleaves the peptide bond of the target protein after aspartic acid present at the primary specificity site, or P1 position, in the specific amino acid sequence.
There are two types of apoptotic caspases&#8212;initiator caspases and executioner or effector caspases.
Both types of caspases are synthesized as procaspases, the inactive precursors.
Each initiator monomer contains a catalytic domain with large and small subunits and an adaptor-binding domain.
Death signals bring the initiator procaspases close to each other, causing dimerization. The dimerization induces interchain cleavage resulting in the activation of the initiator caspase.&#160;
The initiator caspases activate the dimeric effector procaspases by splitting them at the linker region.
The effector caspases then target different cellular proteins, such as cytoskeletal proteins, which eventually results in apoptosis.

caspases

Caspases

Caspase, a family of cysteine proteases, serve as effectors in apoptosis. The ced3 gene in C.elegans was first identified to be involved in apoptosis. This gene encodes the ced-3 caspase that is similar to the interleukin-1-beta converting enzyme or ICE in mammals. In addition to apoptosis, caspases also function in the inflammatory response. Inflammatory caspases are essential in activating pro-inflammatory cytokines that recruit immune cells and block the replication of pathogens inside cells.
Caspase Activation
Caspases are produced as inactive zymogens, called procaspases. The procaspases contain four loops, L1 to L4. During activation, L2 is cleaved, and the monomeric subunits dimerize. The initiator procaspases also have long pro-domains such as the death effector domain (DED) or caspase recruitment domain (CARD). These pro-domains interact with the adaptor molecules to cleave and activate the initiator caspases. Conversely, executioner caspases have short pro-domains and are cleaved by the active initiator caspases.
Caspases and Homeostasis
Cell proliferation and cell death are both essential to maintain homeostasis in multicellular organisms. The over- and under-activation of caspases, thus, can lead to many diseases. For example, decreased caspase activity is a common feature of cancerous cells. Many infectious diseases also decrease caspase activity. For example, the p35 protein released by certain viruses binds the caspases, thus preventing caspase activation and blocking apoptosis. In contrast, the over-activation of inflammatory caspases causes sepsis due to increased inflammatory response. Excessive activation of caspases can also cause diseases such as Alzheimer&#39;s, Parkinson&#8217;s, and Huntington&#39;s.

Caspase, a family of cysteine proteases, serve as effectors in apoptosis. The ced3 gene in C.elegans was first identified to be involved in apoptosis. ...

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JoVE Core

Cell Biology

Unit 1

Cell Death

KEY TERMS AND CONCEPTS

caspases in apoptosis and immunity

Caspases are cysteine proteases that help control cell death and immune defense. They act as effectors in apoptosis, which is the process of programmed cell death. The ced-3 gene in C. elegans was first linked to apoptosis, and it encodes a caspase similar to the interleukin-1-beta converting enzyme, or ICE, in mammals.

Caspases also have a role in inflammation. Inflammatory caspases activate pro-inflammatory cytokines, which help recruit immune cells and stop pathogens from replicating inside cells. This makes caspases important in both cell removal and the body’s response to infection.

Caspases are made first as inactive zymogens called procaspases. These precursors contain four loops, labeled L1 to L4. When activation begins, L2 is cleaved and the subunits dimerize, or pair up, to form the active enzyme.

Initiator procaspases have long pro-domains such as the death effector domain, or DED, and the caspase recruitment domain, or CARD. These pro-domains bind adaptor molecules that help cleave and activate the initiator caspases. Executioner caspases have short pro-domains and are activated by the initiator caspases.

Cell proliferation and cell death must stay balanced to maintain homeostasis in multicellular organisms. When caspase activity is too low, or too high, disease can result. Decreased caspase activity is common in cancer cells, and some viruses release the p35 protein, which binds caspases and blocks apoptosis. Too much inflammatory caspase activity can contribute to sepsis, and excessive caspase activity has also been linked to Alzheimer’s, Parkinson’s, and Huntington’s diseases.

Caspases in Apoptosis and Immunity

overview of cell death

Cell Death Pathways in Cells

Cell death pathways help the body remove old or damaged cells. Cell growth and cell death must stay balanced. If this balance is disrupted, it may contribute to cancer or autoimmune diseases. Cell death was first noticed in the early 19th century, but experimental proof came later. In 1842, Carl Vogt described cell death in a metamorphic toad. At that time, the process was not yet called cell death. Scientists identified separate cell death pathways in the 20th century after advances in...

apoptosis

Apoptosis and Cell Survival Control

Apoptosis is a controlled form of cell death that helps keep tissues healthy. The term comes from two Greek words, apo and ptosis, which mean separation and falling off. Hippocrates used the word to describe gangrene caused by bandaging fractured bones. Apoptosis was separated from necrosis in 1970 after John Kerr described its distinct shape changes. In one experiment, loss of blood supply to liver tissue caused the tissue to shrink. Under an electron microscope, Kerr saw that hepatocytes had...

Caspases are cysteine proteases that help control cell death and immune defense. They act as effectors in apoptosis, which is the process of programmed cell death. The ced-3 gene in C. elegans was first linked to apoptosis, and it encodes a caspase similar to the interleukin-1-beta converting enzyme, or ICE, in mammals. Caspases also have a role in inflammation. Inflammatory caspases activate pro-inflammatory cytokines, which help recruit immune cells and stop pathogens from replicating inside...

the extrinsic apoptotic pathway

How Immune Cells Trigger Cell Death

The extrinsic apoptotic pathway is a cell death process started by signals from outside the cell. In this pathway, extracellular death signals such as specific cytokines activate death receptors on the cell surface. Natural killer cells, or NK cells, and cytotoxic T-lymphocytes help carry out this response. NK cells are part of the innate immune response, while cytotoxic T-lymphocytes belong to the adaptive immune response. These cells recognize receptors on altered cells and activate...

the intrinsic apoptotic pathway

How Cells Trigger Apoptosis from Damage

Intrinsic apoptosis is the cell’s built-in death response to internal stress. Cell injury, hypoxia, and DNA damage can start this process. The B-cell lymphoma 2, or Bcl-2, family of proteins is the main regulator of this pathway. When DNA is damaged, checkpoint proteins such as Ataxia Telangiectasia Mutated, or ATM, and Checkpoints Factor-2, or Chk2, become active. They phosphorylate p53, a protein that helps control cell survival. p53 then turns on pro-apoptotic proteins such as Bax, Bak,...

phagocytosis of apoptotic cells

How Apoptotic Cells Are Cleared

Apoptotic cells must be cleared quickly so they do not cause inflammation, autoimmune disease, or necrosis. During apoptosis, cells break into apoptotic bodies that are then removed by phagocytosis, the process in which other cells engulf and digest them. Professional phagocytes, such as macrophages and immature dendritic cells, handle this job most effectively. Some non-professional phagocytes, including epithelial cells and fibroblasts, can also take part, but they are less efficient. Normal...

autophagic cell death

Autophagy and Cell Death Pathways

Autophagy is a cell cleanup process that can also lead to cell death. Christian de Duve discovered autophagy, in which cell parts are enclosed in membrane-bound sacs called autophagosomes. These autophagosomes then fuse with lysosomes, which digest the material inside. In many cells, autophagy helps prevent cell death. When damage becomes too severe to repair, however, the process can shift toward cell death. Autophagy can connect to apoptosis, necroptosis, and autosis, so it sits at an...

necrosis

Necrosis and Other Cell Death Pathways

Necrosis is an accidental form of cell death that ends in cell lysis, or cell bursting. Rudolf Virchow first used the term in 1859 in his book Cell Pathology to describe advanced tissue breakdown. In high school biology, necrosis is often used to compare damaged cells with other ways cells can die. Necrotic cells can look different depending on the tissue and the cause of injury. In coagulative necrosis, cells lose their nuclei but keep their basic shape because the enzymes that digest cell...

key terms and concepts

Explore how caspases control programmed cell death, inflammation, and disease. Learn about procaspase activation, initiator and executioner caspases, and homeostasis.

Caspases in Apoptosis and Immunity | JoVE K12

cell biology

JoVE Core Cell Biology illustrates complex cellular processes in easy-to-understand yet comprehensive animated video lessons. This collection focuses on the essential components and functions of cells, including organelles and membranes, cellular transport, and cell energetics. It is complemented by scientist-in-action videos that demonstrate the application of cell biology in real-world research experiments.

Caspases in Apoptosis and Immunity

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