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The Intrinsic Apoptotic Pathway

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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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The Extrinsic Apoptotic Pathway

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Related Experiment Video

Updated: Sep 10, 2025

Analysis of Apoptosis in Zebrafish Embryos by Whole-mount Immunofluorescence to Detect Activated Caspase 3

Analysis of Apoptosis in Zebrafish Embryos by Whole-mount Immunofluorescence to Detect Activated Caspase 3

Published on: December 20, 2013

Z-DNA-binding protein 1-mediated programmed cell death: Mechanisms and therapeutic implications.

Yuwei Huang^1,2, Lian Wang^1,2, Yanghui Zhu^1,2

¹Department of Dermatology, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China.

Chinese Medical Journal

|August 25, 2025

Summary

Z-DNA-binding protein 1 (ZBP1) regulates programmed cell death (PCD) pathways, impacting immunity and disease. Targeting ZBP1-mediated PCD offers potential therapeutic strategies for various human conditions.

Keywords:

Apoptosis Necroptosis PANoptosis Programmed cell death Pyroptosis Receptor-interacting protein kinase 3 (RIPK3)Z-DNA-binding protein 1

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Published on: May 3, 2024

Area of Science:

Molecular Biology
Immunology
Cell Biology

Background:

Programmed cell death (PCD) is vital for organismal homeostasis and immunity.
Dysregulation of PCD contributes to various human diseases.
Z-DNA-binding protein 1 (ZBP1) is a key cytosolic sensor involved in multiple PCD pathways.

Purpose of the Study:

To comprehensively review the regulatory functions of ZBP1 in PCD.
To explore ZBP1's interactions with signaling molecules.
To delineate diseases linked to ZBP1-mediated PCD and its therapeutic potential.

Main Methods:

Literature review of ZBP1's role in PCD.
Analysis of ZBP1's interactions with signaling molecules like RIPK3.
Examination of ZBP1's involvement in various pathological conditions.

Main Results:

ZBP1, through its Zα and RHIM domains, senses nucleic acids and regulates apoptosis, necroptosis, pyroptosis, and PANoptosis.
ZBP1 interacts with RIPK3 and influences cell fate.
ZBP1 plays a critical role in infections, inflammatory diseases, neurological disorders, and cancer.

Conclusions:

ZBP1 is a central regulator of diverse PCD pathways with significant implications in disease.
Targeting ZBP1-mediated PCD presents a promising therapeutic avenue.
Further research in disease models may uncover novel therapeutic strategies for ZBP1-related conditions.