Related Experiment Video

Updated: Mar 11, 2026

Lighting Up the Pathways to Caspase Activation Using Bimolecular Fluorescence Complementation
08:47

Lighting Up the Pathways to Caspase Activation Using Bimolecular Fluorescence Complementation

Published on: March 5, 2018

9.5K

Palmitoylation of caspase-6 by HIP14 regulates its activation

Niels H Skotte1, Shaun S Sanders1, Roshni R Singaraja1,2,3

  • 1Centre for Molecular Medicine and Therapeutics, Department of Medical Genetics, Child and Family Research Institute, University of British Columbia, Vancouver, BC, Canada.

Cell Death and Differentiation
|December 3, 2016
PubMed

Insights

Caspase-6 (CASP6) activation, crucial in neurodegenerative diseases, is inhibited by palmitoylation, a newly identified modification. This finding offers potential therapeutic targets for conditions like Alzheimer's and Huntington's disease.

Area of Science:

  • Neuroscience
  • Molecular Biology
  • Biochemistry

Background:

  • Caspase-6 (CASP6) plays a significant role in axonal degeneration observed in neuronal apoptosis and neurodegenerative conditions such as Alzheimer's and Huntington's disease.
  • Elevated CASP6 activity is implicated in stroke and ischemia, suggesting that reducing its activity could restore neuronal function in these diseases.

Purpose of the Study:

  • To investigate the regulatory mechanisms controlling Caspase-6 (CASP6) activation.
  • To identify novel post-translational modifications of CASP6 that influence its activity.

Main Methods:

  • Post-translational modification analysis of Caspase-6 (CASP6).
  • Utilizing Hip14-/- mice and YAC128 mice models.
  • Employing molecular modeling to predict the structural impact of palmitoylation on CASP6.

Main Results:

  • Caspase-6 (CASP6) undergoes post-translational palmitoylation mediated by the enzyme HIP14.
  • Palmitoylation of CASP6 was found to inhibit its activation.
  • Reduced palmitoylation of CASP6 was observed in Hip14-/- and YAC128 mouse models, correlating with increased CASP6 activity.
  • Molecular modeling suggests palmitoylation inhibits CASP6 activation through steric hindrance and by preventing dimerization.

Conclusions:

  • Palmitoylation is identified as a novel post-translational modification of Caspase-6 (CASP6).
  • This modification acts as a key regulator, inhibiting CASP6 activation.
  • Targeting the palmitoylation of CASP6 presents a potential therapeutic strategy for neurodegenerative diseases and conditions involving increased CASP6 activity.

More Related Videos

Measuring Caspase Activity Using a Fluorometric Assay or Flow Cytometry05:29

Measuring Caspase Activity Using a Fluorometric Assay or Flow Cytometry

Published on: March 24, 2023

5.7K
Measuring Composition of CD95 Death-Inducing Signaling Complex and Processing of Procaspase-8 in this Complex07:17

Measuring Composition of CD95 Death-Inducing Signaling Complex and Processing of Procaspase-8 in this Complex

Published on: August 2, 2021

3.0K

Related Concept Videos

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...
14.4K
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...
13.5K
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...
9.0K
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...
9.1K
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...
6.1K
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...
9.0K