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Updated: Aug 7, 2026

Identification of Novel CK2 Kinase Substrates Using a Versatile Biochemical Approach
11:11

Identification of Novel CK2 Kinase Substrates Using a Versatile Biochemical Approach

Published on: February 21, 2019

The kinase CK1α coordinates the initiation and termination of the cGAS-STING pathway

Jane Jardine1,2, Marine Tarrillon1,2, Gwennan André-Grégoire1,2,3

  • 1CRCI2NA, Nantes Université, INSERM, CNRS, Université d'Angers, Nantes, France.

Cell Death and Differentiation
|August 5, 2026
PubMed

Insights

Casein Kinase 1 alpha (CK1α) uniquely regulates the cGAS-STING pathway. CK1α enhances DNA sensing while limiting immune signaling, offering a novel therapeutic target for cancer treatment.

Area of Science:

  • Immunology
  • Molecular Biology
  • Oncology

Background:

  • The cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway is crucial for innate immunity and DNA sensing.
  • This pathway has complex roles in cancer, potentially inhibiting or promoting tumor progression.
  • Understanding the regulation of cGAS-STING is vital for developing cancer therapies.

Purpose of the Study:

  • To identify novel regulators of the cGAS-STING pathway.
  • To elucidate the mechanisms by which Casein Kinase 1 alpha (CK1α) modulates cGAS-STING signaling.
  • To explore the therapeutic potential of targeting CK1α in cancer.

Main Methods:

  • Proteomic approaches to identify CK1α as a cGAS-STING regulator.
  • Investigated CK1α's role in cGAS degradation via the Cullin-RING ubiquitin ligase 3 (CRL3) complex.
  • Assessed CK1α's impact on STING agonist-induced IRF3 activation.
  • Utilized molecular-glue degraders for selective CK1α degradation in cancer cell lines.

Main Results:

  • CK1α acts as a bimodal regulator of the cGAS-STING pathway.
  • CK1α prevents proteasome-dependent degradation of cGAS, enhancing DNA sensing.
  • CK1α inhibits STING-mediated signal propagation and IRF3 activation.
  • Selective CK1α degradation reduced aberrant cGAS-STING signaling in triple-negative breast cancer cells.
  • CK1α degradation combined with a STING agonist promoted apoptosis in acute myeloid leukemia cells.

Conclusions:

  • CK1α's dual role in the cGAS-STING pathway presents a promising therapeutic target.
  • Targeting CK1α offers a potential strategy for modulating innate immune responses in cancer.
  • Further research into CK1α modulation could lead to novel cancer treatments.

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