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Updated: Jul 1, 2025

Experimental Analysis of Apoptotic Thymocyte Engulfment by Macrophages
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SAM68 directs STING signaling to apoptosis in macrophages

Demi van der Horst1, Naziia Kurmasheva1, Mikkel H S Marqvorsen1

  • 1Department of Biomedicine, Aarhus University, Høegh Guldbergsgade 10, 8000, Aarhus C, Denmark.

Communications Biology
|March 7, 2024
PubMed

Insights

Scientists discovered SAM68 is crucial for STING-mediated apoptosis, a key innate immune response to DNA. This process occurs independently of gene transcription, highlighting a novel pathway in cellular defense.

Area of Science:

  • Immunology
  • Cell Biology
  • Molecular Biology

Background:

  • DNA sensing by cGAS-STING pathway triggers innate immunity.
  • STING activation induces type I interferon, inflammatory genes, and apoptosis.
  • The precise mechanisms of STING-induced apoptosis are not fully understood.

Purpose of the Study:

  • To elucidate the molecular mechanisms of STING-dependent apoptosis.
  • To identify key proteins involved in STING-mediated apoptosis.
  • To investigate the role of SAM68 in STING signaling.

Main Methods:

  • Mass spectrometry to identify interacting proteins.
  • Analysis of STING-dependent apoptosis induction.
  • Investigation of IRF3-mediated pathways.
  • Studies on protein trafficking and localization.

Main Results:

  • STING-dependent apoptosis in macrophages utilizes the intrinsic mitochondrial pathway, mediated by IRF3 and independent of gene transcription.
  • SAM68 was identified as a crucial protein for STING-induced apoptosis.
  • SAM68 is essential for full apoptosis activation but not for STING-mediated IFN or NF-κB activation.
  • SAM68 is recruited to STING upon activation, with association occurring at the Golgi or post-Golgi compartments.

Conclusions:

  • SAM68 is a critical mediator of STING-dependent apoptosis.
  • This study reveals a novel non-transcriptional pathway for STING-induced apoptosis involving SAM68.
  • Identifies SAM68 as a STING-interacting protein essential for DNA-activated innate immune responses.

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