ubikwitynacj

Ubikwitynacja, also known as ubiquitination, is a cellular process that attaches the small protein ubiquitin to substrate proteins. This modification influences protein stability, activity, localization, and interactions, and is a key component of the ubiquitin–proteasome system.

The attachment is carried out by a cascade of three enzyme classes. An E1 activating enzyme first activates ubiquitin, an E2 conjugating enzyme carries it, and an E3 ligase transfers ubiquitin to specific substrate proteins, providing substrate specificity. The process is reversible through deubiquitinases (DUBs) that remove ubiquitin.

Ubiquitin can be attached as a single unit (monoubiquitination) or as chains (polyubiquitination). The type of linkage within the polyubiquitin chain determines the outcome: Lys48-linked chains commonly signal proteasomal degradation, while Lys63-linked and other atypical linkages participate in signaling, endocytosis, DNA repair, and trafficking. Different E3 ligases and DUBs confer enormous specificity.

Function and relevance: Ubiquitination regulates cell cycle, immune responses, metabolism, and stress signaling. Malfunctions in the ubiquitin system are linked to cancer, neurodegenerative diseases, and inflammatory disorders. Therapeutic strategies include proteasome inhibitors and inhibitors of specific E3 ligases or DUBs.

History: The ubiquitin–proteasome system was elucidated in the 1980s and 1990s, with a Nobel Prize awarded in 2004 to Aaron Ciechanover, Avram Hershko, and Irwin Rose for its discovery.