Casein kinase 2

Casein Kinase 2 (CK2) is a serine/threonine-specific protein kinase that is essential for various cellular processes. It is known for its ability to phosphorylate a wide range of substrates, including casein, from which it derives its name. CK2 is ubiquitously expressed in all eukaryotic cells and is involved in cell cycle control, DNA repair, transcription, and translation. Its activity is critical for the regulation of cell growth and survival, making it a significant subject of study in cancer research.

Structure

CK2 is a heterotetrameric enzyme composed of two catalytic subunits (α and/or α') and two regulatory β subunits. The α and α' subunits contain the kinase activity and are highly similar, but not identical, allowing for a diversity of substrate recognition. The β subunits are responsible for the stability of the enzyme and can modulate its activity. The quaternary structure of CK2 facilitates its interaction with a broad range of substrates and regulatory proteins.

Function

The primary function of CK2 is the phosphorylation of serine or threonine residues in proteins. This post-translational modification can alter the activity, localization, or stability of the substrate proteins. CK2 is involved in the regulation of several critical cellular processes, including:

• Cell cycle progression: CK2 phosphorylates proteins that are key regulators of the cell cycle, thereby influencing cell division.
• Apoptosis: CK2 can inhibit apoptosis by phosphorylating and inactivating components of the apoptotic machinery, contributing to cell survival.
• DNA repair: CK2 phosphorylates proteins involved in the DNA damage response, aiding in the repair of damaged DNA and maintaining genomic stability.
• Transcription and translation: CK2 modulates the activity of transcription factors and components of the translation machinery, affecting gene expression at multiple levels.

Regulation

The activity of CK2 is regulated by various mechanisms, including autophosphorylation, interaction with cellular proteins, and localization within the cell. Unlike many other kinases, CK2 is constitutively active and does not require activation by external signals. However, its substrate specificity and activity can be modulated by interactions with other proteins and by changes in its subcellular localization.

Clinical Significance

Due to its role in cell growth and survival, CK2 has been implicated in the development and progression of cancer. Overexpression and dysregulation of CK2 have been observed in various types of cancer, making it a potential target for cancer therapy. Inhibitors of CK2 are being explored as therapeutic agents to suppress tumor growth and sensitize cancer cells to conventional therapies.

Research

Research on CK2 continues to uncover its diverse roles in cellular processes and its potential as a therapeutic target. Studies are focused on identifying specific substrates of CK2, understanding its regulation and interaction with other cellular components, and developing specific inhibitors that can modulate its activity in diseases.

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