Informace o publikaci
Mechanism of regulation of lymphoid cell migration persistence by casein kinase 1
| Autoři | |
|---|---|
| Rok publikování | 2025 |
| Druh | Konferenční abstrakty |
| Fakulta / Pracoviště MU | |
| Citace | |
| Popis | Casein kinase 1 (CK1) is a family of serine-threonine kinases mainly known for their function in Wnt and cell polarity pathways. We have previously shown that the inhibition of CK1 in leukemic B-cells decreases their migration and has a significant clinical potential for therapy of common leukemic diseases such as chronic lymphocytic leukemia (CLL) and acute myeloid leukemia (AML). Using novel highly specific inhibitors and degraders, we have also shown that loss of CK1 is connected to loss of migration persistence in these cells. Based on live-cell imaging experiments and phosphoproteomic analysis, we here propose a molecular mechanism of this effect: CK1 takes part in phosphorylation of microtubule +tip complex proteins including CLIP1, CLASP1-2 and SLAIN2. We propose that the impaired formation of +tip complexes leads to loss of leading edge stability and consequently loss of persistence similar to previously described effects of nocodazole. In line with this theory, CK1 inhibition follows similar trends to nocodazole treatment in altering the balance of intracellular tubulin pools. Together with other studies showing the role of CK1 in mitosis, we hope this data may lead to better understanding of how CK1 and therefore also Wnt signalling may influence downstream cytoskeleton rearrangements and alter migratory properties of cells. |
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