Review: A silent concert in developing plants: Dynamic assembly of cullin-RING ubiquitin ligases

Abstract

Plants appear quiet: quietly, they break the ground, expand leaves, search for resources, alert each other to invaders, and heal their own wounds. In contrast to the stationary appearance, the inside world of a plant is full of movements: cells divide to increase the body mass and form new organs; signaling molecules migrate among cells and tissues to drive transcriptional cascades and developmental programs; macromolecules, such as RNAs and proteins, collaborate with different partners to maintain optimal organismal function under changing cellular and environmental conditions. All these activities require a dynamic yet appropriately controlled molecular network in plant cells. In this short review, we used the regulation of cullin-RING ubiquitin ligases (CRLs) as an example to discuss how dynamic biochemical processes contribute to plant development. CRLs comprise a large family of modular multi-unit enzymes that determine the activity and stability of diverse regulatory proteins playing crucial roles in plant growth and development. The mechanism governing the dynamic assembly of CRLs is essential for CRL activity and biological function, and it may provide insights and implications for the regulation of other dynamic multi-unit complexes involved in fundamental processes such as transcription, translation, and protein sorting in plants.

Keywords: Adaptive responses; Developmental plasticity; E3 ligases; Molecular dynamics; Ubiquitination.

Figure 1.

Regulation of protein stability and plant development by cullin-RING ubiquitin ligases (CRLs). (A) Composition of a CRL mediating targeted protein ubiquitination. A stable CRL is formed when the cullin (CUL)-RING core binds an SRM. Ubiquitination occurs when CUL is neddylated, a substrate is recognized and recruited by the SRM, and E2~Ub is engaged by the RING protein. This biochemical process regulates the stability of many regulators participating in key cellular events. SRM: substrate receptor module; Sub: substrate; R: RING protein; N8: NEDD8; Ub: ubiquitin; E2~Ub: ubiquitin E2 conjugating enzyme loaded with ubiquitin. (B) Dynamic regulation of CRL assembly and activity. CAND1 constantly recycles CUL•RING from un-neddylated CRLs and makes the CUL•RING accessible to all SRMs in the cell. Through this dynamic process, SRMs loaded with substrates are timely recruited to the CUL•RING enzymatic core, after which the newly assembled CRL is activated by neddylation and the bound substrate is ubiquitinated. After the ubiquitinated substrate is degraded by the proteasome, the CRL is de-neddylated by CSN and is then allowed to be regulated by CAND1. This CAND1-mediated dynamic cycling of CUL•RING enables rapid assembly of new CRLs in response to the emergence of ubiquitination substrates, and thereby, sustains an adaptive repertoire of CRLs that afford plasticity in molecular signaling and plant development. CSN: COP9 signalosome; CAND1: Cullin-Associated and Neddylation-Dissociated protein 1.