CK1 Is a Druggable Regulator of Microtubule Dynamics and Microtubule-Associated Processes.

Abstract

Protein kinases of the Casein Kinase 1 family play a vital role in the regulation of numerous cellular processes. Apart from functions associated with regulation of proliferation, differentiation, or apoptosis, localization of several Casein Kinase 1 isoforms to the centrosome and microtubule asters also implicates regulatory functions in microtubule dynamic processes. Being localized to the spindle apparatus during mitosis Casein Kinase 1 directly modulates microtubule dynamics by phosphorylation of tubulin isoforms. Additionally, site-specific phosphorylation of microtubule-associated proteins can be related to the maintenance of genomic stability but also microtubule stabilization/destabilization, e.g., by hyper-phosphorylation of microtubule-associated protein 1A and RITA1. Consequently, approaches interfering with Casein Kinase 1-mediated microtubule-specific functions might be exploited as therapeutic strategies for the treatment of cancer. Currently pursued strategies include the development of Casein Kinase 1 isoform-specific small molecule inhibitors and therapeutically useful peptides specifically inhibiting kinase-substrate interactions.

• Authors: Aileen Roth, Adrian Gihring, Joachim Bischof, Leiling Pan, Franz Oswald, Uwe Knippschild
• Journal: Cancers (Cancers (Basel)) Vol. 14 Issue 5 (Mar 05 2022) ISSN: 2072-6694 [Print] Switzerland
• PMID: 35267653 (Publication Type: Journal Article, Review)