ubiquititin

Ubiquititin is a small, highly conserved 76-amino acid protein found ubiquitously in eukaryotic cells. Its primary role is to regulate protein degradation through the ubiquitin-proteasome system (UPS), an essential pathway for maintaining cellular proteostasis. Ubiquitin attaches to target proteins through a process called ubiquitination, which involves the sequential action of three enzymes: E1 (activating enzyme), E2 (conjugating enzyme), and E3 (ligase). This attachment typically occurs via an isopeptide bond between the carboxyl group of ubiquitin's terminal glycine and lysine residues on substrate proteins.

Polyubiquitination, where chains of ubiquitin molecules are linked together, often signals proteins for degradation by the 26S proteasome, a large proteolytic complex. Monoubiquitination, or addition of a single ubiquitin molecule, can also regulate cellular processes such as DNA repair, endocytosis, and signaling pathways. The versatility of ubiquitin signaling is due to the different linkage types and chain architectures that can be formed, which are recognized by various ubiquitin-binding proteins.

Ubiquitin is encoded by multiple genes in the human genome, producing several isoforms and precursors that are processed into mature ubiquitin. Its highly conserved nature across species underscores its fundamental importance in cell biology. Disruptions in ubiquitin pathways are associated with various diseases, including neurodegenerative disorders, cancers, and immune system dysfunctions. Due to its central role in protein turnover and regulation, ubiquitin remains a significant focus of research in cell biology and therapeutic development.