Related Experiment Video

Updated: Jun 12, 2026

Identification of Mediators of T-cell Receptor Signaling via the Screening of Chemical Inhibitor Libraries
08:49

Identification of Mediators of T-cell Receptor Signaling via the Screening of Chemical Inhibitor Libraries

Published on: January 22, 2019

ASK1-JNK signaling cascade mediates Ad-ST13-induced apoptosis in colorectal HCT116 cells

Min Yang1, Mingcan Yu, Dongyin Guan

  • 1Department of Biochemistry and Molecular Biology, Shanghai Medical College, Fudan University, Shanghai 200032, China.

Journal of Cellular Biochemistry
|June 1, 2010
PubMed

Insights

Heat shock protein co-factor ST13, delivered via adenovirus (Ad-ST13), triggers colorectal cancer cell death by activating the ASK1-JNK pathway. This study elucidates ST13

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Oncology

Background:

  • Heat shock protein co-factor ST13 shows potential in colorectal cancer treatment.
  • The precise molecular mechanisms of ST13-induced apoptosis remain unclear.

Purpose of the Study:

  • To investigate the molecular pathways through which ST13 mediates apoptosis in colorectal cancer cells.
  • To determine the role of specific signaling kinases in Ad-ST13-induced apoptosis.

Main Methods:

  • Adenovirus-mediated delivery of ST13 (Ad-ST13) in human colorectal HCT116 cells.
  • Analysis of apoptosis signal-regulating kinase 1 (ASK1), c-Jun N-terminal kinase (JNK), p38, and extracellular signal-regulated kinase (ERK) phosphorylation.
  • Assessment of AP-1 transcription activity, cytochrome c release, and caspase activation.
  • Investigation of the interaction between ST13 and ASK1 using their tetratricopeptide repeat (TPR) domains.

Main Results:

  • Ad-ST13 activates ASK1 and JNK, but not p38, in HCT116 cells.
  • ERK phosphorylation increase is attributed to adenovirus replication, not ST13.
  • ST13 overexpression enhances AP-1 transcription activity.
  • Inhibition of the ASK1-JNK pathway reduces Ad-ST13-mediated apoptosis, cytochrome c release, and caspase activation.
  • Direct interaction between ST13 and ASK1 was confirmed.

Conclusions:

  • Ad-ST13 induces colorectal cancer cell apoptosis primarily through the ASK1-JNK signaling cascade.
  • ST13 interacts with ASK1, suggesting a direct role in initiating the apoptotic signaling pathway.
  • Understanding this mechanism provides a basis for developing ST13-based cancer therapies.

More Related Videos

Multiomics Analysis of TMEM200A as a Pan-Cancer Biomarker07:47

Multiomics Analysis of TMEM200A as a Pan-Cancer Biomarker

Published on: September 15, 2023

Related Concept Videos

Role Of Notch Signalling In Intestinal Stem Cell Renewal01:12

Role Of Notch Signalling In Intestinal Stem Cell Renewal

Notch signaling was first discovered in Drosophila melanogaster, where it is involved in cell lineage differentiation. Notch signaling regulates the maintenance and differentiation of intestinal stem cells or ISCs by controlling the expression of atonal homolog 1 or Atoh1. Atoh1 directs cells to differentiate into secretory cells.
Direct cell-to-cell contact is needed for the activation of Notch signaling. The signal is initiated when a notch ligand binds to a receptor on an adjacent cell, also...
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...
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...
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...
Intracellular Signaling Affects Focal Adhesions01:17

Intracellular Signaling Affects Focal Adhesions

Integrins act both as extracellular input receivers and as intracellular processing activators. As their name suggests, integrins are entirely integrated into the membrane structure. Their hydrophobic membrane-spanning regions interact with the phospholipid bilayer's hydrophobic region. These membrane receptors provide extracellular attachment sites for effectors like hormones and growth factors. They activate intracellular response cascades when their effectors are bound and active.
Some...
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...