Apoptosis Extracellular Signals

Apoptosis, or programmed cell death, is a vital process that regulates cellular health and development by eliminating damaged, superfluous, or potentially harmful cells. This controlled cell elimination is triggered by various extracellular signals, including death ligands like tumor necrosis factor (TNF), Fas ligand (FasL), and TNF-related apoptosis-inducing ligand (TRAIL). These ligands interact with their respective death receptors on the cell surface, initiating a signaling cascade that activates caspase enzymes, leading to the execution of apoptosis. This pathway ensures that cells respond appropriately to external stimuli and stresses, maintaining tissue integrity and preventing uncontrolled cell proliferation.

In addition to direct signaling through death receptors, apoptosis can be triggered by environmental changes such as growth factor withdrawal or hormonal imbalances. For example, the absence of essential growth factors can disrupt mitochondrial function, leading to the release of pro-apoptotic factors like cytochrome c into the cytoplasm and initiating the intrinsic apoptotic pathway. Similarly, hormones like glucocorticoids can induce apoptosis in specific cells, such as lymphocytes, aiding in the regulation of the immune response and adaptation to physiological stresses.

Moreover, apoptosis is influenced by interactions with the extracellular matrix (ECM). Anoikis, a form of apoptosis triggered by cell detachment from the ECM, prevents detached cells from proliferating inappropriately, which is crucial for preventing cancer metastasis. The precise regulation of apoptosis by extracellular signals is critical for health and disease management, highlighting potential therapeutic targets in treating conditions where apoptosis is dysregulated, such as in autoimmune diseases, neurodegeneration, and various cancers.

Figure 1 Signal transduction leading to apoptosis. (Rennekampff, 2021)

Representative Targets in Apoptosis Extracellular Signals

FASLG

FASLG, commonly known as Fas Ligand, is a type-II transmembrane protein that belongs to the tumor necrosis factor (TNF) family and plays a pivotal role in the regulation of the immune system and induction of apoptosis. FASLG binds to its receptor, Fas (also known as CD95), which is expressed on various cell types, including lymphocytes. This binding triggers a cascade of events leading to the formation of the death-inducing signaling complex (DISC) and subsequent activation of caspases, which are critical enzymes in the execution phase of apoptosis. The FAS/FASLG system is crucial for the maintenance of immune system homeostasis and the prevention of autoimmune diseases. It helps regulate the immune response by inducing the death of activated immune cells, thus preventing them from becoming autoreactive. FASLG also plays a role in immune privilege, a mechanism that protects certain sites of the body (like the eye and brain) from immune system attack, by inducing apoptosis in invading immune cells. Dysregulation of FASLG has been implicated in a variety of disorders. Inadequate expression can lead to immune system disorders, where the body fails to properly eliminate autoreactive or overactive immune cells, potentially resulting in autoimmune diseases. Conversely, excessive expression of FASLG has been associated with the destruction of beneficial cells, contributing to conditions like AIDS, where an excessive immune response leads to the depletion of T-cells.

Recommended Humanized Anti-FASLG mAb (CAT#: TAB-261CL)

Figure 2 Anti-Human FASLG Recombinant Antibody (TAB-261CL) in ELISA. ELISA analysis of TAB-261CL was performed by coating with human FASLG protein (His Tag). The secondary antibody: HRP-anti-human IgG.

Recommended Human Anti-FASLG mAb (CAT#: HPAB-0179CQ)

Figure 3 Human Anti-FASLG Recombinant Antibody (HPAB-0179CQ) in ELISA. ELISA analysis of HPAB-0179CQ was performed by coating with human FASLG protein (His Tag). The secondary antibody: HRP-anti-human IgG.

GZMB

GZMB, or Granzyme B, is a serine protease released by cytotoxic T lymphocytes and natural killer (NK) cells, key components of the immune system responsible for the destruction of virally infected cells and tumor cells. Granzyme B is stored within the granules of these cytotoxic cells and is released during an immune response, usually in conjunction with the protein perforin, which facilitates the entry of granzyme B into target cells. Once inside the target cell, Granzyme B initiates apoptosis, a programmed cell death process, by cleaving and activating caspases, particularly caspase-3. This cascade leads to rapid cell death, effectively removing cells that are dangerous or no longer needed by the body. Additionally, Granzyme B can directly cleave other cellular substrates, contributing to apoptosis through various pathways, including the disruption of mitochondrial integrity and the activation of DNA damage responses. The role of Granzyme B in immune surveillance and defense makes it a critical factor in controlling viral infections and the proliferation of cancer cells. However, dysregulation of Granzyme B activity can lead to pathological conditions. For instance, excessive or misdirected activity of Granzyme B is implicated in some autoimmune diseases, where it may contribute to the destruction of healthy cells and tissues. Conversely, insufficient Granzyme B activity can result in inadequate immune responses, allowing persistent infections and cancer cells to evade immune detection.

Recommended Rabbit Anti-GZMB mAb (CAT#: ZG-0701J)

Figure 4 Rabbit Anti-GZMB Antibody (ZG-0701J) in IF. Immunofluorescence staining of Hela Cells with this product at 1:50, counter-stained with DAPI. The cells were fixed in 4% formaldehyde, permeated by 0.2% TritonX-100, and blocked in 10% normal Goat Serum. The cells were then incubated with the antibody overnight at 4°C. Nuclear DNA was labeled in blue with DAPI. The secondary antibody was FITC-conjugated Goat Anti-Rabbit IgG (H+L).

TIMP3

TIMP3, or Tissue Inhibitor of Metalloproteinases 3, is one of the four members of the TIMP family that regulates the activity of matrix metalloproteinases (MMPs). TIMP3 is unique among the TIMPs in that it is tightly bound to the extracellular matrix (ECM) and inhibits not only MMPs but also a disintegrin and metalloproteinase (ADAM) and ADAM with thrombospondin motifs (ADAMTS) families of enzymes. These proteases are involved in the breakdown of the extracellular matrix, which is crucial for normal tissue remodeling, repair, and angiogenesis. TIMP3 plays a critical role in maintaining tissue homeostasis by inhibiting the excessive proteolytic activity of MMPs, ADAMs, and ADAMTSs. By regulating these enzymes, TIMP3 helps control processes such as ECM degradation, which is critical during wound healing and in the maintenance of tissue structure. Dysregulation of TIMP3 expression and function has been linked to a variety of pathological conditions including cardiovascular diseases, such as atherosclerosis and heart failure, where imbalance in ECM remodeling contributes to disease progression. In addition to its roles in cardiovascular health, TIMP3 is also significant in the pathogenesis of cancer and ocular diseases. In cancer, decreased levels of TIMP3 can lead to increased tumor growth and metastasis due to enhanced ECM degradation and altered cell migration. Conversely, in ocular diseases like age-related macular degeneration (AMD), overexpression of TIMP3 is thought to contribute to abnormal extracellular matrix accumulation and choroidal neovascularization.

Full List of Targets in Apoptosis Extracellular Signals

Tested Data-Supported Products for Targeting Apoptosis Extracellular Signals

CAT	Product Name	Biomarker	Assay	Image
TAB-261CL	Anti-Human FASLG Recombinant Antibody	FASLG	WB
HPAB-0179CQ	Human Anti-FASLG Recombinant Antibody (clone 4G11)	FASLG	WB
ZG-0701J	Rabbit Anti-GZMB Recombinant Antibody (clone 6A1)	GZMB	IHC

For research use only. Not intended for any clinical use.