Jove
Visualize
Contact Us
JoVE
x logofacebook logolinkedin logoyoutube logo
ABOUT JoVE
OverviewLeadershipBlogJoVE Help Center
AUTHORS
Publishing ProcessEditorial BoardScope & PoliciesPeer ReviewFAQSubmit
LIBRARIANS
TestimonialsSubscriptionsAccessResourcesLibrary Advisory BoardFAQ
RESEARCH
JoVE JournalMethods CollectionsJoVE Encyclopedia of ExperimentsArchive
EDUCATION
JoVE CoreJoVE BusinessJoVE Science EducationJoVE Lab ManualFaculty Resource CenterFaculty Site
Terms & Conditions of Use
Privacy Policy
Policies

Related Concept Videos

MAPK Signaling Cascades01:07

MAPK Signaling Cascades

Mitogen-activated protein kinase, or MAPK pathway, activates three sequential kinases to regulate cellular responses such as proliferation, differentiation, survival, and apoptosis. The canonical MAPK pathway starts with a mitogen or growth factor binding to an RTK. The activated RTKs stimulate Ras, which recruits Raf or MAP3 Kinase (MAPKKK), the first kinase of the MAPK signaling cascade. Raf further phosphorylates and activates MEK or MAP2 Kinases (MAPKK), which in turn phosphorylates MAP...
The Ras Gene02:38

The Ras Gene

The Ras-gene-encoded proteins are regulators of signaling pathways controlling cell proliferation, differentiation, or cell survival. The Ras-gene family in humans constitutes three primary members—the HRas, NRas, and KRas. These genes code for four functionally distinct yet closely related proteins—the HRas, NRas, KRas4A, and KRas4B. The involvement of mutant Ras genes in human cancer was first discovered in 1982 and is among the most common causes of human tumorigenesis.
Ras is a superfamily...
PI3K/mTOR/AKT Signaling Pathway01:22

PI3K/mTOR/AKT Signaling Pathway

The mammalian target of rapamycin  (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1  (mTORC1) and mTOR complex 2  (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast,  mTORC2 consists of a rapamycin-insensitive companion...
Small GTPases - Ras and Rho01:24

Small GTPases - Ras and Rho

Ras and Rho are small monomeric GTPases that act downstream of receptor tyrosine kinase (RTK) and regulate various cellular processes. These GTPases switch between active and inactive states by binding to guanine nucleotides.
Three regulatory proteins control their activity:
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...
Regulation of the Unfolded Protein Response01:31

Regulation of the Unfolded Protein Response

Inositol-requiring kinase one or IRE1 is the most conserved eukaryotic unfolded protein response (UPR) receptor. It is a type I transmembrane protein kinase receptor with a distinctive site-specific RNase activity. As the binding mechanics of the misfolded proteins with the N-terminal domain of IRE-1 are unclear, three binding models — direct, indirect, and allosteric -- are proposed for receptor activation. Nevertheless, it is known that once a misfolded protein associates with IRE1, it...

You might also read

Related Articles

Articles linked to this work by shared authors, journal, and citation graph.

Sort by
Same author

JAAD CME Part 1: Mechanism of Action of GLP-1 Receptor Agonists and Potential Pathways in Skin Health.

Journal of the American Academy of Dermatology·2026
Same author

Lipopolysaccharide-induced cytokine signaling activates a temporal innate defense program and represses pancreatic β-cell identity.

The Journal of biological chemistry·2025
Same author

Nitric oxide attenuates PI4P accumulation at the ER membrane to inhibit encephalomyocarditis virus replication selectively in β-cells.

The Journal of biological chemistry·2025
Same author

BET bromodomain inhibitors attenuate transcription of a subset of IL-1-induced NF-κB targets that promote inflammation in β-cells.

The Journal of biological chemistry·2025
Same author

Role of SIRT3 in the regulation of Gadd45α expression and DNA repair in β-cells.

The Journal of biological chemistry·2025
Same author

CCN2 functions as a modulator of cell cycle regulation in human dermal fibroblasts.

Journal of cell communication and signaling·2025

Related Experiment Video

Updated: Jul 19, 2026

Tyramide Signal Amplification for the Immunofluorescent Staining of ZBP1-Dependent Phosphorylation of RIPK3 and MLKL After HSV-1 Infection in Human Cells
09:15

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

Zinc induces ERK-dependent cell death through a specific Ras isoform.

Claudette Klein1, Kimberly Creach, Virginia Irintcheva

  • 1Department of Biochemistry and Molecular Biology, School of Medicine, Saint Louis University, Saint Louis, MO, USA. kleinc@slu.edu

Apoptosis : an International Journal on Programmed Cell Death
|October 3, 2006
PubMed
Summary

Zinc ions trigger apoptosis in embryonic fibroblasts, even without p53. This cell death pathway is ERK-dependent and specifically involves H-Ras activation, offering new insights into zinc

More Related Videos

Identification of EGFR and RAS Inhibitors using Caenorhabditis elegans
08:12

Identification of EGFR and RAS Inhibitors using Caenorhabditis elegans

Published on: October 5, 2020

Identification of Transcription Factor Regulators using Medium-Throughput Screening of Arrayed Libraries and a Dual-Luciferase-Based Reporter
11:32

Identification of Transcription Factor Regulators using Medium-Throughput Screening of Arrayed Libraries and a Dual-Luciferase-Based Reporter

Published on: March 27, 2020

Related Experiment Videos

Last Updated: Jul 19, 2026

Tyramide Signal Amplification for the Immunofluorescent Staining of ZBP1-Dependent Phosphorylation of RIPK3 and MLKL After HSV-1 Infection in Human Cells
09:15

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

Identification of EGFR and RAS Inhibitors using Caenorhabditis elegans
08:12

Identification of EGFR and RAS Inhibitors using Caenorhabditis elegans

Published on: October 5, 2020

Identification of Transcription Factor Regulators using Medium-Throughput Screening of Arrayed Libraries and a Dual-Luciferase-Based Reporter
11:32

Identification of Transcription Factor Regulators using Medium-Throughput Screening of Arrayed Libraries and a Dual-Luciferase-Based Reporter

Published on: March 27, 2020

Area of Science:

  • Cell Biology
  • Biochemistry
  • Toxicology

Background:

  • p53 is a key tumor suppressor involved in cell death.
  • Zinc's role in cell death mechanisms is not fully understood.
  • Apoptosis can occur through p53-dependent or p53-independent pathways.

Purpose of the Study:

  • To investigate the mechanism of zinc-induced cell death in p53-deficient cells.
  • To determine the role of the Ras/ERK pathway in zinc-mediated apoptosis.
  • To identify the specific Ras isoform activated by zinc.

Main Methods:

  • Utilized IIC9 embryonic fibroblasts (p53-minus).
  • Administered zinc and the ionophore pyrithione to induce cell death.
  • Assessed apoptosis using relevant assays.
  • Investigated the Ras/ERK signaling pathway, including dominant-negative Ras expression and Raf-RBD pull-down assays.

Main Results:

  • Zinc induces apoptosis in p53-minus IIC9 cells.
  • The cell death pathway is dependent on ERK activation.
  • Zinc treatment specifically activates H-Ras, not N-Ras.
  • Dominant-negative Ras expression inhibits zinc-induced ERK activation and cytotoxicity.

Conclusions:

  • Intracellular zinc initiates a p53-independent apoptotic response.
  • Zinc-mediated cell death relies on the activation of the Ras/ERK pathway.
  • H-Ras isoform specificity distinguishes zinc-induced Ras activation from other stimuli.