Deubiquitylating enzymes and their emerging role in plant biology

Abstract

Ubiquitylation is a reversible post-translational modification that is involved in various cellular pathways and that thereby regulates various aspects of plant biology. For a long time, functional studies of ubiquitylation have focused on the function of ubiquitylating enzymes, especially the E3 ligases, rather than deubiquitylating enzymes (DUBs) or ubiquitin isopeptidases, enzymes that hydrolyze ubiquitin chains. One reason may be the smaller number of DUBs in comparison to E3 ligases, implying the broader substrate specificities of DUBs and the difficulties to identify the direct targets. However, recent studies have revealed that DUBs also actively participate in controlling cellular events and thus play pivotal roles in plant development and growth. DUBs are also essential for processing ubiquitin precursors and are important for recycling ubiquitin molecules from target proteins prior to their degradation and thereby maintaining the free ubiquitin pool in the cell. Here, we will discuss the five different DUB families (USP/UBP, UCH, JAMM, OTU, and MJD) and their known biochemical and physiological roles in plants.

Keywords: DUB; JAMM; MJD; OTU; UBP; UCH; USP; deubiquitylation.

FIGURE 1

Cellular function of DUBs. (A) Ubiquitin is translated as tandem ubiquitin repeats with several amino acid extension (depicted as X) at the C-terminus or as fusion to ribosomal proteins in plants. DUBs process the peptide bond between ubiquitin and its fusion protein to produce ubiquitin monomers that can be then conjugated to its substrate proteins. (B) DUBs can remove ubiquitin chains from its target proteins and recycle ubiquitin molecules prior to degradation by the 26S proteasome (left) or before the sequestration into the intraluminal vesicles of the multivesicular body (right). Deubiquitylation can start at the distal end as shown here or at the proximal end or in the interior of polyubiquitin chains. (C) Removal of the ubiquitin chains by DUBs can inhibit their recognition by the degradation machinery and thus rescues them from degradation regardless whether the protein is a cytosolic proteasomal substrate (left) or a membrane cargo (right). (D) Ubiquitylation can serve as an interaction signal for the modified protein. By removing the ubiquitin moiety, DUBs could change the binding affinity of its target protein to another protein, either by enabling (left) or by disabling the binding of the unmodified protein to its interacting protein.

FIGURE 2

Phylogenetic analyses of Arabidopsis UBP-, JAMM-, and OTU-domain proteinases. A Neighbor-Joining consensus tree based on amino acid sequences surrounding the catalytic domain for Arabidopsis UBP- (A), JAMM- (B) and OTU- (C) domain proteins is shown. Scale bars indicate 0.5 aa substitutions per site. DUBs mentioned in the text are highlighted in blue. Note that CSN5A and CSN5B shown in (B) are deneddylating- and not deubiquitylating enzymes.