Encoding and Decoding Ubiquitin Chain Architectures: Fine-Tuning the Fate of Proteins

Ubiquitin modifications are a central hub for numerous biomolecular reactions, finely tuning essential processes such as protein degradation and cellular signal transduction. The architecture of ubiquitin chains—linkage types, branching patterns, and lengths—encodes a rich layer of information, referred to as the ubiquitin code. This intricate code orchestrates diverse biological outcomes. Notably, earlier studies have revealed that branched ubiquitin chains accelerate proteasomal degradation. Yet, the delicate molecular choreography that drives this enhancement remains a mystery, waiting to be fully unraveled. Recent structural, biochemical, and chemical biology approaches have provided new insights into the molecular mechanisms underlying the encoding and decoding of branched ubiquitin chain. In this review, we focus on the proteolytic codes of K11/K48-, K29/K48-, and K48/K63-branched ubiquitin chains, offering an overview of recent research and discussing future challenges and prospects.