Related Experiment Video

Updated: May 22, 2026

Measuring Endoplasmic Reticulum Stress and Unfolded Protein Response in HIV-1 Infected T-Cells and Analyzing its Role in HIV-1 Replication
10:12

Measuring Endoplasmic Reticulum Stress and Unfolded Protein Response in HIV-1 Infected T-Cells and Analyzing its Role in HIV-1 Replication

Published on: June 14, 2024

CK2 regulates ATF4 and CHOP transcription within the cellular stress response signalling pathway

Carolin C Schneider1, Emmanuel Ampofo, Mathias Montenarh

  • 1Medizinische Biochemie und Molekularbiologie und Kompetenzzentrum Molekulare Medizin (KOMM), Universität des Saarlandes, Homburg, Saarland 66424, Germany. c.schneidercaro@web.de

Cellular Signalling
|May 22, 2012
PubMed

Insights

Inhibition of protein kinase CK2 induces cancer cell death by activating the amino acid response pathway, primarily through the CHOP gene's amino acid response element (AARE). This highlights a novel therapeutic strategy targeting cancer cell apoptosis.

Area of Science:

  • Molecular Biology
  • Cancer Biology
  • Cellular Stress Response

Background:

  • Protein kinase CK2 is elevated in tumors, protecting cancer cells from apoptosis.
  • CK2 inhibition induces programmed cell death, making it a cancer therapy target.
  • Previous studies indicated CHOP (C/EBP-homologous protein) induction and ER stress are crucial for apoptosis in LNCaP cells after CK2 inhibition.

Purpose of the Study:

  • To investigate which specific promoter element of the CHOP gene is responsible for its induction following CK2 inhibition.
  • To elucidate the signaling pathway activated by CK2 inhibition leading to apoptosis.

Main Methods:

  • Utilized mutated reporter constructs of the CHOP promoter to analyze the role of different promoter elements.
  • Investigated the activation of various CHOP promoter elements in response to CK2 inhibition.
  • Analyzed the expression of transcription factors involved in ER stress signaling.

Main Results:

  • The amino acid response element (AARE) was identified as the most prominent element for CHOP induction after CK2 inhibition.
  • The ER stress element and AP-1 binding site played minor or no role in CHOP induction.
  • Up-regulation of the transcription factor ATF4 was observed after CK2 inhibition, which is known to signal through the AARE.

Conclusions:

  • CK2 inhibition triggers apoptosis in cancer cells primarily through the activation of the amino acid response pathway.
  • The AARE within the CHOP promoter is the key mediator of this response.
  • ATF4 acts as a crucial transcription factor in this pathway, reinforcing the role of amino acid response signaling.

More Related Videos

A Chromatin Immunoprecipitation Assay to Identify Novel NFAT2 Target Genes in Chronic Lymphocytic Leukemia09:52

A Chromatin Immunoprecipitation Assay to Identify Novel NFAT2 Target Genes in Chronic Lymphocytic Leukemia

Published on: December 4, 2018

Related Concept Videos

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...
NF-κB-dependent Signaling Pathway02:26

NF-κB-dependent Signaling Pathway

The transcription factor NF-κB was discovered in 1986 in the lab of Nobel laureate Professor David Baltimore, for its interaction with the immunoglobulin light chain enhancer in B-cells. After more than three decades of study, it is now evident that NF-κB regulates the expression of over 100 genes. Most of these genes play an essential role in the innate and adaptive immune responses as well as the inflammatory responses of animals.
NF-κB-dependent Signaling Mechanism
The heterodimer of NF-κB...
Other Stress Responses in Bacteria01:30

Other Stress Responses in Bacteria

Bacteria have global regulatory systems that control several types of stress mechanisms. These include Pho regulon and the heat shock response, which are essential systems for environmental adaptation, such as nutrient limitation and proteotoxic stress. The Pho regulon and the heat shock response exemplify bacterial resilience, enabling rapid adaptation to fluctuating environmental conditions.Pho RegulonBacteria require phosphorus for essential cellular processes, including nucleic acid...
cAMP-dependent Protein Kinase Pathways01:25

cAMP-dependent Protein Kinase Pathways

Cyclic Adenosine Monophosphate (cAMP) is an essential second messenger that activates protein kinase A (PKA) and regulates various biological processes. A single epinephrine molecule binds to GPCR and activates several heterotrimeric G proteins, each stimulating multiple adenylyl cyclase, amplifying the signal, and synthesizing large numbers of cAMP molecules. Small changes in cAMP concentration affect PKA activity. The binding of four cAMP molecules induces a conformational change in PKA,...
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...
DNA Damage can Stall the Cell Cycle02:36

DNA Damage can Stall the Cell Cycle

In response to DNA damage, cells can pause the cell cycle to assess and repair the breaks. However, the cell must check the DNA at certain critical stages during the cell cycle. If the cell cycle pauses before DNA replication, the cells will contain twice the amount of DNA. On the other hand, if cells arrest after DNA replication but before mitosis, they will contain four times the normal amount of DNA. With a host of specialized proteins at their disposal,cells must use the right protein at...