The ubiquitin (Ub)-26S proteasome system (UPS) is a selectively proteolytic system that targets the ubiquitylation and turnover of short-lived proteins, as well as a number of abnormal proteins, accumulated during cellular metabolism, inside a eukaryotic cell. Genomic studies and recent proteomic analyses have proven the UPS an important regulatory system that rivals transcription in gene expression regulation.

The system starts the activation of Ub, a 76-amino acid small peptide, by a Ub activating enzyme (E1).  The activated Ub is then conjugated to a second enzyme, called the ubiquitin-conjugating enzyme (E2).  An E2, functioning as a Ub deliverer, either directly transfers the Ub onto an Ub ligating enzyme (E3) or in many cases, works together with an E3 to ligate the Ub onto the ε-amino group of a lysine residue in a ubiquitylation substrate.  Several Ubs can be tandemly concatenated through further ubiquitylation reactions to form a poly Ub chain.  In many cases, poly-ubiquitylated substrates are recognized and degraded by a 2.5 MDa protein complex, the 26S proteasome.  

In addition to the proteolytic function, mono-ubiquitylation and some types of poly-ubiquitylation with different topologies of poly Ub chains regulate localizations and/or activities of ubiquitylation substrates.

In plants, a handful of research programs has demonstrated that the UPS regulates a wide array of developmental and physiological processes, including hormone responses, the cell cycle, stress/pathogen responses, circadian rhythm, and plant reproduction.

Due to the breadth and the depth of the UPS and ubiquitylation substrates, it is extremely challenging to decode the functions of this gigantic group using canonical reverse or forward genetics approaches.  We use an integrated plant omics approach to deal with these >3,000 genes instead.

  • We use evolutionary and computational biology approaches to study how natural selection fixed the functions of individual UPS genes.
  • We use proteomics to fish UPS regulons.
  • We use high-throughput phenomics to tackle the functions of individual UPS regulatory networks.
  • We use reverse genetics and biochemistry to demonstrate novel molecular mechanisms of the UPS.
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