Ubikitiinijärjestelmällä

Ubikitiinijärjestelmällä, often referred to as the ubiquitin-proteasome system (UPS), is a fundamental cellular process responsible for the regulated degradation of proteins in eukaryotic cells. This complex pathway plays a critical role in maintaining cellular homeostasis, regulating numerous biological processes, and responding to various cellular stresses.

The process begins with the covalent attachment of ubiquitin, a small regulatory protein, to target proteins. This ubiquitination is a multi-step enzymatic cascade involving three key types of enzymes: ubiquitin-activating enzymes (E1s), ubiquitin-conjugating enzymes (E2s), and ubiquitin ligases (E3s). E1s activate ubiquitin in an ATP-dependent manner. Activated ubiquitin is then transferred to an E2 enzyme, which in turn, with the assistance of an E3 ligase, facilitates the transfer of ubiquitin to a specific substrate protein. E3 ligases are crucial for conferring substrate specificity to the process.

A single ubiquitin molecule attached to a protein can signal for its degradation or alter its function. However, the most common signal for degradation is the formation of a polyubiquitin chain, typically linked through lysine 48 of ubiquitin. This polyubiquitinated protein is then recognized by the 26S proteasome, a large multi-subunit protease complex. The proteasome unfolds the tagged protein, translocates it into its catalytic core, and degrades it into small peptides.

The ubiquitin-proteasome system is involved in a wide array of cellular functions, including cell cycle progression, DNA repair, signal transduction, protein quality control, and immune responses. Dysregulation of the UPS has been implicated in the pathogenesis of various diseases, such as cancer, neurodegenerative disorders (e.g., Parkinson's and Alzheimer's disease), and infectious diseases. Consequently, the UPS is a significant target for therapeutic interventions.