Related Experiment Video

Updated: Dec 6, 2025

Author Spotlight: A Selective Luciferase-Based Assay for Monitoring ATG4B 27 Activity in Cells
09:51

Author Spotlight: A Selective Luciferase-Based Assay for Monitoring ATG4B 27 Activity in Cells

Published on: June 30, 2023

1.3K

DAPK3 inhibits gastric cancer progression via activation of ULK1-dependent autophagy

Guan-Man Li1,2, Lei Li3, Meng-Qing Li4

  • 1Laboratory of General Surgery, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, China.

Cell Death and Differentiation
|October 10, 2020
PubMed

Insights

Death-associated protein kinase 3 (DAPK3) suppresses gastric cancer by activating autophagy. DAPK3 directly phosphorylates ULK1, promoting cell death and improving patient survival outcomes.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Cell Death Pathways

Background:

  • Dysregulated cell proliferation and death are hallmarks of cancer.
  • Death-associated protein kinase 3 (DAPK3) is frequently downregulated in gastric cancer (GC), correlating with poor prognosis.
  • The precise mechanism of DAPK3's tumor-suppressive role is not fully understood.

Purpose of the Study:

  • To elucidate the molecular mechanism of DAPK3-mediated tumor suppression in gastric cancer.
  • To investigate the role of DAPK3 in regulating programmed cell death, specifically autophagy.
  • To determine if DAPK3 acts as a prognostic marker in GC.

Main Methods:

  • Mass spectrometry to identify DAPK3 interacting proteins.
  • In vitro kinase assays to assess DAPK3 activity.
  • Immunoprecipitation to confirm protein interactions and phosphorylation events.
  • Analysis of clinical gastric cancer samples for DAPK3 and ULK1 Ser556 phosphorylation co-expression.

Main Results:

  • DAPK3 directly phosphorylates ULK1 at Ser556, increasing its kinase activity.
  • DAPK3-mediated ULK1 phosphorylation enhances ULK1 complex formation, VPS34 complex activation, and autophagy induction.
  • Both DAPK3 kinase activity and ULK1 Ser556 phosphorylation are essential for DAPK3's tumor suppressive effects.
  • Co-expression of DAPK3 and phosphorylated ULK1 (Ser556) in GC patients correlates with better survival.

Conclusions:

  • DAPK3 exerts tumor-suppressive functions in gastric cancer through the autophagy pathway.
  • DAPK3 is a novel regulator of autophagy, directly activating ULK1 via phosphorylation.
  • DAPK3 and ULK1 Ser556 phosphorylation represent a potential prognostic biomarker for gastric cancer.

More Related Videos

Author Spotlight: Genetic Profiling for Fluorouracil Response in Gastric Cancer06:21

Author Spotlight: Genetic Profiling for Fluorouracil Response in Gastric Cancer

Published on: May 10, 2024

1.0K
Author Spotlight: Exploring Salidroside's Molecular Mechanisms in Breast Cancer Treatment11:13

Author Spotlight: Exploring Salidroside's Molecular Mechanisms in Breast Cancer Treatment

Published on: June 9, 2023

2.0K

Related Concept Videos

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...
4.9K
mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
4.5K
Inhibition of Cdk Activity02:34

Inhibition of Cdk Activity

The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
5.4K
Autophagy01:27

Autophagy

Autophagy is a self-digesting process by which a cell protects itself from threats both within and outside the cell, ranging from abnormal proteins to invading bacteria. In this process, obsolete components of the cell and invading microbes are degraded by hydrolytic enzymes active in an acidic environment of the lysosomal lumen.
An autophagic pathway consists of a series of signaling events activated in response to diverse stress and physiological conditions such as food deprivation,...
5.5K
Tumor Progression02:07

Tumor Progression

Tumor progression is a phenomenon where the pre-formed tumor acquires successive mutations to become clinically more aggressive and malignant. In the 1950s, Foulds first described the stepwise progression of cancer cells through successive stages.
Colon cancer is one of the best-documented examples of tumor progression. Early mutation in the APC gene in colon cells causes a small growth on the colon wall called a polyp. With time, this polyp grows into a benign, pre-cancerous tumor. Further...
7.0K
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...
7.5K