Composition, roles, and regulation of cullin-based ubiquitin e3 ligases

Abstract

Due to their sessile nature, plants depend on flexible regulatory systems that allow them to adequately regulate developmental and physiological processes in context with environmental cues. The ubiquitin proteasome pathway, which targets a great number of proteins for degradation, is cellular tool that provides the necessary flexibility to accomplish this task. Ubiquitin E3 ligases provide the needed specificity to the pathway by selectively binding to particular substrates and facilitating their ubiquitylation. The largest group of E3 ligases known in plants is represented by CULLIN-REALLY INTERESTING NEW GENE (RING) E3 ligases (CRLs). In recent years, a great amount of knowledge has been generated to reveal the critical roles of these enzymes across all aspects of plant life. This review provides an overview of the different classes of CRLs in plants, their specific complex compositions, the variety of biological processes they control, and the regulatory steps that can affect their activities.

Figure 1.

The Ubiquitin Proteasome Pathway and plant cullin-based E3 ligases. (A) Model of the ubiquitin proteasome pathway and (B–E) the four cullin-based E3 ligases found within plants. (B) SCF E3 ligases are composed of SKP1-like protein and an F-box containing protein that work together to bind to the CUL1 protein as well as facilitate targeting of specific substrates. Additionally (C) CRL3 and (D) CRL4 complex utilize variety of adapter proteins in order to bind with the cullin in addition to the target substrate. CRL3 utilizing a single adaptor protein that contains a BTB/POZ domain while CRL4 complexes are similar to SCF complexes due to the use of two proteins, DDB1 and a DCAF protein, in order to target substrates and assembly with the cullin protein. (E) The APC/C complex shows a greater diversity compare to the other classes of cullin-based E3 ligases due to the nature of this complex to utilize at least 11 subunits in addition to using a cullin- and an RBX1-like protein (APC2 and APC11 respectively) as the core scaffolding unit.

Figure 2.

SCF complexes participate in a wide variety of plant processes.

Figure 3.

CRL3 complexes and their roles in plant processes.

Figure 4.

CRL4 complexes play a wide role in plant processes.

Figure 5.

The APC/C complex and its functional role in plants.

Figure 6.

CRL regulation by CAND1 and NEDD8. CAND1 functions as a substrate adaptor exchange factor, facilitating the formation of a dynamic cellular pool of CRLs. Once assembled, the cullin subunit is neddylated. If no substrate is available, the CRL is rapidly deneddylated, returning the CRL to the CAND1 cycle. Alternatively, the presence of substrate promotes CRL activity by inhibiting CSN-mediated deneddylation. Upon substrate depletion by the 26S proteasome, the CSN deneddylates the cullin and the CRL is disassembled by CAND1, enabling new CRLs to form. N8 = NEDD8.

Figure 7.

Overview of CRL complex functions in various plant processes.