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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.

Apoptosis

Apoptosis

Apoptosis is a combination of two Greek words, 'apo' and 'ptosis,' meaning separation and falling off, respectively. Hippocrates used this word to describe gangrene, which was caused due to bandaging of fractured bones. Apoptosis was distinguished from necrosis in 1970 when John Kerr reported observations of morphological changes occurring during apoptosis. During one experiment, he observed that the disruption of blood supply to the liver tissue resulted in a size reduction of the tissue.

Export of Misfolded Proteins out of the ER

Export of Misfolded Proteins out of the ER

After folding, the ER assesses the quality of secretory and membrane proteins. The correctly folded proteins are cleared by the calnexin cycle for transport to their final destination, while misfolded proteins are held back in the ER lumen. The ER chaperones attempt to unfold and refold the misfolded proteins but sometimes fail to achieve the correct native conformation. Such terminally misfolded proteins are then exported to the cytosol by ER-associated degradation or ERAD pathway for...

Lysosomal Hydrolases

Lysosomal Hydrolases

Lysosomes are the site for the degradation of macromolecules and biological polymers released during membrane trafficking events such as secretory, endocytic, autophagic, and phagocytic pathways. The membrane-enclosed area of the lysosome, called the lumen, contains hydrolytic enzymes active in an acidic environment. These acid hydrolases are functional at a pH between 4.5 and 5 and are involved in cellular processes such as cell signaling, energy metabolism, restoration of the plasma membrane,...

Phagocytosis of Apoptotic Cells

Phagocytosis of Apoptotic Cells

Cells undergoing apoptosis form apoptotic bodies that must be removed immediately to prevent inflammation, autoimmune diseases, and necrosis. Phagocytosis is carried out by professional phagocytes such as macrophages or immature dendritic cells. Non-professional phagocytes such as epithelial cells and fibroblasts also take part in this process; however, they are not as effective as professional phagocytes.
Normal cells contain receptors that prevent them from being recognized by phagocytes.

The Intrinsic Apoptotic Pathway

The Intrinsic Apoptotic Pathway

Internal cellular stress, such as cellular injury or hypoxia, triggers intrinsic apoptosis. The B-cell lymphoma 2 (Bcl-2) family of proteins are the primary regulators of the intrinsic apoptotic pathway. For example, during DNA damage, checkpoint proteins, such as Ataxia Telangiectasia Mutated (ATM protein) and Checkpoints Factor-2 (Chk2) proteins, are activated. These proteins phosphorylate p53 which further activates pro-apoptotic proteins, such as Bax, Bak, PUMA, and Noxa, and inhibits...

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Related Experiment Video

Updated: Jun 12, 2026

A High Yield and Cost-efficient Expression System of Human Granzymes in Mammalian Cells

A High Yield and Cost-efficient Expression System of Human Granzymes in Mammalian Cells

Published on: June 10, 2015

Orphan granzymes find a home.

Niels Bovenschen¹, J Alain Kummer

¹Department of Pathology, University Medical Center Utrecht, 3584 CX Utrecht, The Netherlands. n.bovenschen@umcutrecht.nl

Immunological Reviews

|June 12, 2010

Summary

This summary is machine-generated.

Human orphan granzymes (H, K, M) are key players in cytotoxic lymphocyte functions beyond apoptosis. This review details their biology, including roles in immune regulation and inflammation.

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Area of Science:

Immunology
Cell Biology
Molecular Biology

Background:

Cytotoxic lymphocytes utilize granule-exocytosis to eliminate tumor and virus-infected cells.
Cytotoxic granules contain perforin and granzymes, serine proteases initiating target cell apoptosis.
Granzymes also perform extracellular functions, including immune regulation and inflammation.

Purpose of the Study:

To review and discuss the current understanding of human orphan granzymes (granzymes H, K, and M).
To highlight the distinct biological characteristics and functions of these less-studied granzymes.

Main Methods:

Literature review of existing research on human granzymes H, K, and M.
Synthesis of data regarding their structure, function, and biological roles.

Main Results:

Human granzyme family comprises five members; granzymes A and B are well-characterized.
Emerging research elucidates the specific characteristics of granzymes H, K, and M (orphan granzymes).
These orphan granzymes exhibit diverse functions beyond direct cytotoxicity.

Conclusions:

Human orphan granzymes (H, K, M) possess unique biological activities.
Further research into orphan granzymes is crucial for a comprehensive understanding of cytotoxic lymphocyte function.
These granzymes are implicated in extracellular matrix degradation, immune regulation, and inflammation.