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Apoptosis signaling pathway: key mechanisms in cell death and survival

What is the apoptosis signaling pathway?

The apoptosis signaling pathway is a tightly regulated biological process responsible for programmed cell death, essential for maintaining tissue homeostasis, immune balance, and normal development. Unlike necrosis, apoptosis eliminates damaged, infected, or unnecessary cells in a controlled, non-inflammatory manner.

Apoptosis is activated in response to intrinsic stress signals or extrinsic death signals and determines whether a cell survives or undergoes irreversible death.

Dysregulation of apoptosis contributes to a wide range of diseases, including cancer, autoimmune disorders, neurodegenerative diseases, and chronic inflammatory conditions.

Apoptosis Pathway qPCR Array by AnyGenes for analyzing gene expression in programmed cell death.

Apoptosis pathway activity can be efficiently assessed by measuring gene expression of core regulators, downstream effectors, and pathway-specific biomarker signatures.

Apoptosis signaling pathway biomarker list
View the genes included in our apoptosis pathway qPCR arrays.

Apoptosis-Pathway
Overview of apoptosis signalling pathways and the effects of pro-survival signalling,
immune cells and the tumour microenvironment

Key takeaways

  • Central mechanism controlling programmed cell death
  • Balances cell survival and elimination
  • Operates through intrinsic, extrinsic, and immune-mediated pathways
  • Strongly linked to cancer, immune diseases, and neurodegeneration
  • Highly suitable for biomarker discovery and gene expression profiling

Major apoptosis signaling pathways

Extrinsic pathway
(death receptor)

The extrinsic pathway is initiated by extracellular ligands binding to death receptors on the cell surface. These receptors belong to the TNF receptor superfamily and include TNFR1, Fas (CD95), and TRAIL receptors.

Ligand binding triggers the formation of the Death-Inducing Signaling Complex (DISC), leading to activation of caspase-8 and downstream effector caspases that execute apoptosis.

Intrinsic pathway
(mitochondrial)

 The intrinsic pathway responds to internal cellular stress such as DNA damage, oxidative stress, oncogene activation, or cytotoxic drugs.

Key events include:

  • Mitochondrial outer membrane permeabilization
  • Release of cytochrome c into the cytosol
  • Formation of the apoptosome (Apaf-1, procaspase-9)
  • Activation of caspase-9, followed by effector caspases

This pathway is tightly regulated by the BCL-2 family of proteins, which control mitochondrial integrity.

Perforin / Granzyme
pathway

This pathway is used by cytotoxic T lymphocytes and NK cells to eliminate infected or malignant cells.

Perforin forms pores in the target cell membrane, allowing granzyme B to enter and directly activate caspases or trigger mitochondrial apoptosis.

Molecular regulation of apoptosis

Crosstalk between pathways

Apoptosis pathways are interconnected. The BH3-only protein Bid links extrinsic and intrinsic pathways when cleaved by caspase-8, amplifying mitochondrial apoptosis.

Execution phase

Effector caspases (such as caspase-3 and caspase-7) degrade cellular structures, leading to:

  • DNA fragmentation
  • Cell shrinkage
  • Formation of apoptotic bodies
    These are subsequently cleared by phagocytes without inflammation.

Regulatory proteins

  • p53: activates apoptosis in response to DNA damage
  • IAPs: inhibit caspases and suppress apoptosis
  • Survivin: promotes cell survival, frequently overexpressed in cancer

Apoptosis versus necrosis

Apoptosis and necrosis represent fundamentally different forms of cell death.
Feature Apoptosis Necrosis
Regulation Controlled Uncontrolled
Inflammation No Yes
Cell morphology Shrinkage, fragmentation Swelling, rupture
Biological role Homeostasis Tissue damage

Apoptosis preserves tissue integrity, whereas necrosis promotes inflammation and injury.

Biological functions of apoptosis

The apoptosis signaling pathway regulates:

  • Tissue homeostasis and development
  • Immune cell selection and tolerance
  • Elimination of damaged or infected cells
  • Prevention of malignant transformation

Apoptosis signaling pathway in disease

Cancer

Cancer cells frequently evade apoptosis through mutations in TP53, overexpression of BCL-2, or dysregulation of caspases, allowing uncontrolled survival and therapy resistance.

Neurodegenerative diseases

Excessive neuronal apoptosis contributes to diseases such as Alzheimer’s, Parkinson’s, and Huntington’s disease.

Autoimmune diseases

Insufficient apoptosis of autoreactive immune cells can lead to diseases such as lupus and rheumatoid arthritis.

Cardiovascular and metabolic diseases

Stress-induced apoptosis contributes to myocardial injury, heart failure, and metabolic dysfunction.

Therapeutic relevance of apoptosis signaling

Because apoptosis determines cell fate, it is a major therapeutic target:

  • Pro-apoptotic therapies in cancer
  • Apoptosis inhibitors in neurodegeneration and ischemia
  • Combination strategies targeting apoptosis and survival pathways

Accurate biomarker profiling of apoptosis signaling is essential for therapy development and response prediction.

Why study the apoptosis signaling pathway with AnyGenes®?

At AnyGenes®, we provide high-performance qPCR arrays and customizable SignArrays® designed for apoptosis pathway analysis.

Our solutions enable researchers to:

  • Quantify apoptosis-related gene expression signatures
  • Analyze intrinsic, extrinsic, and immune-mediated apoptosis
  • Study cross-talk with TNF, p53, NF-κB, and mitochondrial pathways

Generate robust, reproducible, publication-ready data

Apoptosis signaling pathway biomarker analysis with AnyGenes®

What can be analyzed?

  • Death receptors and ligands
  • Caspases and apoptosome components
  • BCL-2 family regulators
  • p53-dependent apoptosis markers
  • Immune-mediated cytotoxicity genes

Customize your own signaling pathways (SignArrays®) with the factors of your choice!
Simply download and complete our Personalized SignArrays® information file and send it at [email protected] to initiate your project.

Frequently asked questions

It is a programmed cell death pathway that removes damaged or unnecessary cells while preserving tissue integrity.

The extrinsic (death receptor), intrinsic (mitochondrial), and perforin/granzyme pathways.

Cancer cells evade apoptosis, enabling uncontrolled growth and therapy resistance.

By measuring expression of pathway regulators and downstream targets using targeted gene expression approaches such as qPCR pathway arrays.

  1. Jan R, Chaudhry GS. Understanding Apoptosis and Apoptotic Pathways Targeted Cancer Therapeutics. Adv Pharm Bull. (2019)1;9(2):205–218.
  2. Pfeffer CM, Singh ATK. Apoptosis: A Target for Anticancer Therapy. Int J Mol Sci. (2018)2;19(2):448.
  3. Adams JM, Cory S. The BCL-2 arbiters of apoptosis and their growing role as cancer targets. Cell Death Differ. (2018);25(1):27-36.
  4. Carneiro BA, El-Deiry WS. Targeting apoptosis in cancer therapy. Nat Rev Clin Oncol. (2020);17(7):395-417.
  5. Kashyap D et al. Intrinsic and extrinsic pathways of apoptosis: Role in cancer development and prognosis. Adv Protein Chem Struct Biol. (2021);125:73-120.
  6. Abdulhussein D et al.  Apoptosis in health and diseases of the eye and brain. Adv Protein Chem Struct Biol. (2021);126:279-306.
  7. Carneiro BA, El-Deiry WS. Targeting apoptosis in cancer therapy. Nat Rev Clin Oncol. (2020);17(7):395-417.
  8. Neophytou CM et al. Apoptosis Deregulation and the Development of Cancer Multi-Drug Resistance. Cancers (Basel). 2021 Aug 28;13(17):4363.

Apoptosis signaling pathway biomarker list

You can check the biomarker list included in this pathway, see below:

Species : Homo sapiens (human)

Human Signaling Pathways

Signaling PathwaysProduct refInformations

Apoptosis

AP1H1

List infos

Apoptosis

AP2H1

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Apoptosis

AP3H1

List infos


Species : Mus musculus (mouse)

Mouse Signaling Pathways

Signaling PathwaysProduct refInformations

Apoptosis

AP1M1

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Apoptosis

AP2M1

List infos

Apoptosis

AP3M1

List infos


Species : Rattus norvegicus (rat)

Rat Signaling Pathways

Signaling PathwaysProduct refInformations

Apoptosis

AP1R1

List infos

Apoptosis

AP2R1

List infos


Species : Sus Scrofa (Pig)

Pig Signaling Pathways

Signaling PathwaysProduct refInformations

Apoptosis

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List In progress...


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