Related Experiment Video

Updated: Jul 22, 2026

Analysis of Apoptosis in Zebrafish Embryos by Whole-mount Immunofluorescence to Detect Activated Caspase 3
08:20

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

Published on: December 20, 2013

ZBP-89-induced apoptosis is p53-independent and requires JNK

L Bai1, S O Yoon, P D King

  • 1Department of Internal Medicine, University of Michigan, Ann Arbor, MI 48109, USA.

Cell Death and Differentiation
|February 14, 2004
PubMed

Insights

ZBP-89 triggers cancer cell death by activating JNK, a key stress response pathway, independent of p53. This study reveals ZBP-89

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Cancer Research

Background:

  • ZBP-89 is implicated in cancer cell apoptosis.
  • The precise molecular mechanisms of ZBP-89-induced apoptosis are not fully understood.
  • Understanding ZBP-89's role in apoptosis can reveal new therapeutic targets.

Purpose of the Study:

  • To elucidate the downstream signaling pathways regulated by ZBP-89 during apoptosis.
  • To identify specific mitogen-activated protein kinase (MAPK) pathways involved in ZBP-89-mediated cell death.
  • To investigate the role of Bcl-2 family proteins in ZBP-89-induced apoptosis.

Main Methods:

  • Ectopic expression of ZBP-89 in human gastrointestinal cancer cells.
  • Pharmacological inhibition of JNK, ERK, and p38 MAP kinases.
  • Analysis of protein phosphorylation and dephosphorylation.
  • Oligonucleotide microarray analysis to assess gene expression changes.
  • Small interfering RNA (siRNA) to silence ZBP-89 expression.

Main Results:

  • ZBP-89 induced apoptosis via the mitochondrial pathway, activating JNK1/2, ERK1/2, and p38 MAP kinases.
  • JNK activation was crucial for ZBP-89-induced apoptosis, while ERK inhibition enhanced it.
  • ZBP-89 repressed the expression of dual-specificity phosphatase MKP6, leading to increased JNK phosphorylation.
  • ZBP-89 downregulated anti-apoptotic proteins Bcl-xL and Mcl-1.

Conclusions:

  • ZBP-89 induces apoptosis in gastrointestinal cancer cells through a p53-independent mechanism.
  • The apoptotic pathway is critically dependent on the activation of JNK signaling.
  • ZBP-89's regulation of MKP6 and Bcl-2 family proteins contributes to its pro-apoptotic function.

More Related Videos

Tyramide Signal Amplification for the Immunofluorescent Staining of ZBP1-Dependent Phosphorylation of RIPK3 and MLKL After HSV-1 Infection in Human Cells09:15

Tyramide Signal Amplification for the Immunofluorescent Staining of ZBP1-Dependent Phosphorylation of RIPK3 and MLKL After HSV-1 Infection in Human Cells

Published on: October 20, 2022

Knockdown of FAM83A to Verify Its Role in Cervical Cancer Cell Growth and Cisplatin Sensitivity04:20

Knockdown of FAM83A to Verify Its Role in Cervical Cancer Cell Growth and Cisplatin Sensitivity

Published on: February 9, 2024

Related Concept Videos

Apoptosis01:30

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.
Caspases01:24

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.
The Extrinsic Apoptotic Pathway01:17

The Extrinsic Apoptotic Pathway

The extrinsic apoptotic pathway is initiated when extracellular death-inducing signals, such as specific cytokines, activate the death receptors expressed on the cell surface. The immune cells involved in this pathway are natural killer cells (NK cells) and cytotoxic T-lymphocytes. NK cells are critical in innate immune response, while cytotoxic T-lymphocytes are associated with adaptive immune response. These cells recognize specific receptors expressed on the altered cells and activate...
The Intrinsic Apoptotic Pathway01:31

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...
Interactions Between Signaling Pathways01:19

Interactions Between Signaling Pathways

Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
The JAK-STAT Signaling Pathway01:20

The JAK-STAT Signaling Pathway

Several cytokine receptors have tightly bound Janus kinase or JAK proteins attached at their cytosolic tail. Small signaling molecules such as cytokines, growth hormones, or prolactins bind to the cytokine receptors and initiate their dimerization. The dimerization brings the cytosolic JAKs together that trans-phosphorylate and activates each other. The activated JAKs now phosphorylate cytosolic tails of the cytokine receptors, which serve as binding sites for adaptor proteins such as  SH2...