Research Explained: Protein kinase CK2: a potential therapeutic target for diverse human diseases

Authors: Christian Borgo, Claudio D’Amore, Stefania Sarno, Mauro Salvi, Maria Ruzzene

Publication Date: May 17, 2021

Research Explained By: Brad Davidson, CSNK2A1 Foundation Science Communication Intern

Link to article: https://www.nature.com/articles/s41392-021-00567-7

Research Explained Summary:

In this review article, the authors summarize all research conducted to date on the protein CK2 (Casein Kinase 2), an aggregate of multiple proteins that form a complex including two copies each of CK2α and CK2β, and how it relates to various human diseases. CK2 is an enzyme, meaning that it causes chemical reactions. Its two sub-components perform different functions – CK2α is the catalytic domain that performs the reaction, while CK2β is a regulatory domain that controls when the reaction happens. Unlike many enzymes that perform chemical reactions within a cell, CK2 does not need to be activated by another protein to perform its function. Generally, CK2 acts on other enzymes that are performing functions such as cell survival, growth, and migration among other functions, further increasing their ability to stimulate cells to perform these actions.

CK2 was first implicated in human disease in 1995 as a pro-cancer molecule due to its higher-than-expected presence in various cancers. Generally, cancers use their high levels of CK2 to promote cell survival and growth, granting them the ability to continue growing in the face things that usually kill cancers, such as the immune system and therapeutics. Other research groups have implicated roles for CK2 in infections, diabetes, cardiovascular diseases, retinal diseases, and inflammatory diseases. In addition, CK2 has been implicated in various neurodegenerative diseases associated with aging, including Parkinson’s, Alzheimer’s, Huntington’s, and Amyotrophic lateral sclerosis (ALS). Furthermore, CK2 has been implicated in a variety of behavioral neurologic disorders including Autism, ADHD, Schizophrenia, Major Depressive Disorder, and most relevant to the CSNK2A1 Foundation, OCNDS. Mutations in the CSNK2A1 gene, which encodes the CK2α subunit of CK2, cause OCNDS. OCNDS is a disease that manifests differently across individuals, but generally leads to symptoms including but not limited to developmental delays, muscular weakness, slow growth, and epilepsy. A similar disorder known as POBINDS caused by mutations in the CSNK2B gene that encodes CK2β has also recently been discovered, with patients displaying similar symptoms to OCNDS but with greater risk of seizure.

In terms of treatment for these various CK2-related diseases, there are multiple CK2 inhibitors currently in clinical trials as anti-cancer drugs. The mechanism of action for CK2 in OCNDS is still unclear, meaning that we don’t know if a CK2 inhibitor would be a promising candidate treatment or if CK2 needs to be targeted in a different way.