Related Experiment Video

Updated: Nov 11, 2025

Tumor Allotransplantation in Drosophila melanogaster with a Programmable Auto-Nanoliter Injector
05:06

Tumor Allotransplantation in Drosophila melanogaster with a Programmable Auto-Nanoliter Injector

Published on: February 2, 2021

2.6K

The tumor suppressor kinase DAPK3 drives tumor-intrinsic immunity through the STING-IFN-β pathway

Mariko Takahashi1, Chan-Wang J Lio1,2, Anaamika Campeau3,4

  • 1La Jolla Institute for Immunology, La Jolla, CA, USA.

Nature Immunology
|March 26, 2021
PubMed

Insights

Death-associated protein kinase 3 (DAPK3) is crucial for anti-tumor immunity by activating the STING pathway. Loss of DAPK3 impairs immune responses and reduces chemo-immunotherapy effectiveness in cancer.

Area of Science:

  • Oncology
  • Immunology
  • Molecular Biology

Background:

  • Cancer cells evade host immunity through complex mechanisms.
  • Understanding the link between oncogenic mutations and immune escape is critical for developing effective cancer therapies.

Purpose of the Study:

  • To identify novel regulators of anti-tumor immunity.
  • To elucidate the role of DAPK3 in the STING pathway and its impact on cancer immune surveillance.

Main Methods:

  • Loss-of-function screening of 1,001 tumor suppressor genes.
  • Assessing STING pathway activation and interferon-beta stimulated gene induction.
  • Analyzing immune cell infiltration and tumor growth in DAPK3-deficient models.
  • Phospho-proteomics to identify key protein interactions and modifications.

Main Results:

  • DAPK3 was identified as a key regulator of the STING pathway.
  • Loss of DAPK3 impaired STING activation, leading to reduced interferon-beta production.
  • DAPK3 deficiency promoted tumor growth and diminished anti-tumor immune cell infiltration.
  • DAPK3 regulates STING post-translational modifications, including K63-linked poly-ubiquitination, crucial for immune signaling.

Conclusions:

  • DAPK3 is essential for STING pathway activation and innate immune responses within tumors.
  • DAPK3 plays a vital role in tumor immune surveillance and response to chemo-immunotherapy.
  • Targeting DAPK3 may offer a novel strategy to enhance anti-tumor immunity.

More Related Videos

Transfer of Manipulated Tumor-associated Neutrophils into Tumor-Bearing Mice to Study their Angiogenic Potential In Vivo08:19

Transfer of Manipulated Tumor-associated Neutrophils into Tumor-Bearing Mice to Study their Angiogenic Potential In Vivo

Published on: July 20, 2019

6.2K
Experimental Melanoma Immunotherapy Model Using Tumor Vaccination with a Hematopoietic Cytokine09:15

Experimental Melanoma Immunotherapy Model Using Tumor Vaccination with a Hematopoietic Cytokine

Published on: February 24, 2023

3.7K

Related Concept Videos

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...
7.3K
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...
10.1K
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...
7.1K
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...
4.5K
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...
4.0K
Interactions Between Signaling Pathways01:19

Interactions Between Signaling Pathways

Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
6.8K