Targeting mitotic regulators in cancer as a strategy to enhance immune recognition.

Eukaryotic DNA has evolved to be enclosed within the nucleus to protect the cellular genome from autoinflammatory responses driven by the immunogenic nature of cytoplasmic DNA. Cyclic GMP-AMP Synthase (cGAS) is the cytoplasmic dsDNA sensor, which upon activation of Stimulator of Interferon Genes (STING), mediates production of pro-inflammatory interferons (IFNs) and interferon stimulated genes (ISGs). However, although this pathway is crucial in detection of viral and microbial genetic material, cytoplasmic DNA is not always of foreign origin.

Functional characterization of C21ORF2 association with the NEK1 kinase mutated in human in diseases.

The NEK1 kinase controls ciliogenesis, mitosis, and DNA repair, and mutations cause human diseases including axial spondylometaphyseal dysplasia and amyotrophic lateral sclerosis. mutations cause a similar pattern of human diseases, suggesting close functional links with Here, we report that endogenous NEK1 and C21ORF2 form a tight complex in human cells. A C21ORF2 interaction domain "CID" at the C-terminus of NEK1 is necessary for its association with C21ORF2 in cells, and pathogenic mutations in this region disrupt the complex.

Phosphoproteomic screening identifies physiological substrates of the CDKL5 kinase.

Mutations in the gene encoding the protein kinase CDKL5 cause a debilitating neurodevelopmental disease termed CDKL5 disorder. The impact of these mutations on CDKL5 function is poorly understood because the substrates and cellular processes controlled by CDKL5 are unclear. Here, we describe a quantitative phosphoproteomic screening which identified MAP1S, CEP131 and DLG5-regulators of microtubule and centrosome function-as cellular substrates of CDKL5.