Development and Discovery of a Selective Degrader of Casein Kinases 1 δ/ε.

Members of the casein kinase 1 (CK1) family have emerged as key regulators of cellular signaling and as potential drug targets. Functional annotation of the 7 human isoforms would benefit from isoform-selective inhibitors, allowing studies on the role of these enzymes in normal physiology and disease pathogenesis. However, due to significant sequence homology within the catalytic domain, isoform selectivity is difficult to achieve with conventional small molecules.

Carboxy-terminal polyglutamylation regulates signaling and phase separation of the Dishevelled protein.

Polyglutamylation is a reversible posttranslational modification that is catalyzed by enzymes of the tubulin tyrosine ligase-like (TTLL) family. Here, we found that TTLL11 generates a previously unknown type of polyglutamylation that is initiated by the addition of a glutamate residue to the free C-terminal carboxyl group of a substrate protein. TTLL11 efficiently polyglutamylates the Wnt signaling protein Dishevelled 3 (DVL3), thereby changing the interactome of DVL3.

Pre-existing cell subpopulations in primary prostate cancer tumors display surface fingerprints of docetaxel-resistant cells.

Purpose: Docetaxel resistance is a significant obstacle in the treatment of prostate cancer (PCa), resulting in unfavorable patient prognoses. Intratumoral heterogeneity, often associated with epithelial-to-mesenchymal transition (EMT), has previously emerged as a phenomenon that facilitates adaptation to various stimuli, thus promoting cancer cell diversity and eventually resistance to chemotherapy, including docetaxel. Hence, understanding intratumoral heterogeneity is essential for better patient prognosis and the development of personalized treatment strategies.

Splice variants of CK1α and CK1α-like: Comparative analysis of subcellular localization, kinase activity, and function in the Wnt signaling pathway.

Members of the casein kinase 1 (CK1) family are important regulators of multiple signaling pathways. CK1α is a well-known negative regulator of the Wnt/β-catenin pathway, which promotes the degradation of β-catenin via its phosphorylation of Ser45. In contrast, the closest paralog of CK1α, CK1α-like, is a poorly characterized kinase of unknown function.